acid-phosphatase and Multiple-Myeloma

In tumors characterized by a high osteotropism, such as multiple myeloma, the measurement of bone metabolism markers is helpful in monitoring both severity and prognosis of the skeletal disease. Here, we review the pathophysiology of these markers including tartrate resistant acid phosphatase (TRAcP), which appears highly specific and closely related to the extent of myeloma bone lesions.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Isoenzymes; Multiple Myeloma; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Antigens; Blood Protein Disorders; Gaucher Disease; Glucosylceramidase; Glucosylceramides; Humans; Hypergammaglobulinemia; Multiple Myeloma

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Bone Marrow; Bone Marrow Cells; Cytoplasmic Granules; Diagnosis, Differential; Eosinophils; Erythrocytes; Esterases; Hematopoietic Stem Cells; Histocytochemistry; Humans; Iron; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Monocytes; Multiple Myeloma; Naphthaleneacetic Acids; Neutrophils; Peroxidases; Plasma Cells; Skin Window Technique; Staining and Labeling

Bisphosphonates have been found to reduce skeletal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, a third-generation aminobisphosphonate, in bone turnover and disease activity in MM patients.. Patients with MM, stage II or III, were randomly assigned to receive either pamidronate 90 mg (group I: 23 patients) or ibandronate 4 mg (group II: 21 patients) as a monthly intravenous infusion in addition to conventional chemotherapy. Skeletal events, such as pathologic fractures, hypercalcaemia, and bone radiotherapy were analysed. Bone resorption markers [N-terminal cross-linking telopeptide of type-I collagen (NTX) and tartrate-resistant acid phosphatase type 5b (TRACP-5b)], bone formation markers (bone alkaline phosphatase and osteocalcin), markers of disease activity (paraprotein, CRP, beta 2-microglobulin), and interleukin-6 (IL-6) were also studied.. In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL-6, paraprotein, CRP, and beta 2-microglobulin from the second month of treatment, having no effect on bone formation. TRACP-5b also had a significant reduction in the pamidronate group from the second month of treatment and in the ibandronate group from the sixth month. However, there was a greater reduction of NTX, IL-6, and beta 2-microglobulin in group I than in group II, starting at the second month of treatment (P = 0.002, 0.001, and 0.004, respectively) and of TRACP-5b, starting at the fourth month (P = 0.014), that being continued throughout the 10-month follow-up of this study. There was no difference in skeletal events during this period. A significant correlation was observed between changes of NTX and changes of TRACP-5b, IL-6, and beta 2-microglobulin from the second month for patients of both groups.. These results suggest that a monthly dose of 90 mg of pamidronate is more effective than 4 mg of ibandronate in reducing osteoclast activity, bone resorption, IL-6, and possibly tumour burden in MM. TRACP-5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM.

Topics: Acid Phosphatase; Aged; Antineoplastic Agents; beta 2-Microglobulin; Biomarkers; Bone Resorption; Collagen; Collagen Type I; Diphosphonates; Female; Humans; Ibandronic Acid; Interleukin-6; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Osteogenesis; Pamidronate; Peptides; Tartrate-Resistant Acid Phosphatase

Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Collagen; Collagen Type I; Disease-Free Survival; Female; Glycoproteins; Humans; Male; Middle Aged; Multiple Myeloma; Multivariate Analysis; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Prognosis; Survival Rate

In 1982 a randomized trial of either alternating or syncopated VMCP/VBAP regimens for the treatment of active multiple myeloma was begun (Southwest Oncology Group Study 8229/30). A concurrent investigation was undertaken to evaluate the clinical importance and significance of cytochemically stainable plasma cell acid phosphatase (AP) and beta-glucuronidase enzymes (BG). Pretreatment bone marrow aspirates were available for analysis from 399 patients for AP and 398 patients for BG. The AP scores ranged between 42 and 395, and the BG scores ranged between 1 and 346. There was a significant increase of AP (P = .001) and BG (P = .002) in multiple myeloma as compared with a set of patients with benign plasmacytosis. The enzyme scores did not significantly relate to Ig idiotype of myeloma or other prognostic variables except that the BG scores varied significantly with the level of albumin (P = .03) and hemoglobin (P = .01). Analysis of patient groups with different levels of enzyme scores showed that 61 of 398 patients with an AP score of less than 130 had a poorer median survival of 1.7 versus 2.8 years for patients with higher scores (P = .001). In the multivariate analysis of survival, low AP score was an important prognostic factor (P = .006), but BG did not contribute significantly. It is suggested that the subset of patients presenting with low AP should be considered for specialized or more aggressive therapy.

Topics: Acid Phosphatase; Glucuronidase; Histocytochemistry; Humans; Multiple Myeloma; Multivariate Analysis; Plasma Cells; Prognosis; Survival Rate

To explore the significance of serum bone metabolic markers in the diagnosis and monitoring of multiple myeloma bone disease(MBD).. Thirty-six newly diagnosed multiple myeloma (MM) patients who were treated in Department of Hematology, Tianjin Medical University General Hospital from January 2013 to December 2014 were collected. Bone morbidity was graded into two stages according to the radiographic evaluation of the skeleton: stage A (n=12) included patients with no lytic lesions or with osteoporosis alone; stage B (n=24) included patients with osteolytic lesions and/or a pathological fracture. All the patients achieved partial or complete remission after treated with bortezomib + dexamethasone + zoledronic acid regimen. A total of 25 aged- and gender-matched healthy individuals were enrolled in this study as controls. The levels of serum tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin (OCN), and procollagen I amino-terminal propeptide (PINP) were investigated by ELISA and electrochemiluminescence immunoassay (ECLIA). The differences of these bone metabolic markers before and after treatment, and at different stages of bone disease were observed.. The value of TRACP-5b in the newly diagnosed MM was significantly higher than that in the healthy controls and after treatment(median 4.16 vs 2.63 U/L, P=0.014; 4.16 vs 2.61 U/L, P=0.037). Serum level of CTX in the newly diagnosed MM patients was significantly decreased after treatment (median: 0.26 vs 1.05 µg/L, P=0.003). The ratio of CTX/OCN and CTX/PINP decreased after treatment, but there were no significant differences (both P>0.05). The pretreatment level of serum TRACP-5b in stage B patients was higher than that of the healthy controls (median: 4.20 vs 2.63 U/L, P=0.015). The levels of serum CTX in stage A and stage B patients were both higher than that of the healthy controls (median: 1.16 vs 0.48 µg/L, P=0.002; 0.88 vs 0.48 µg/L, P=0.040). The levels of serum OCN and PINP were higher in stage A patients compared with stage B patients, but there were no significant differences (both P>0.05). The ratio of CTX/OCN and CTX/PINP of stage A and stage B patients all increased compared with those of the healthy controls, but there were no significant differences (all P>0.05).. Bone damage of MM patients is improved after effective treatment, but bone imbalance still exists, indicating that the treatment of MBD is a long process. Abnormal serum levels of TRACP-5b and CTX are found before positive X-ray findings in MBD, suggesting that these biochemical markers could be used as indices for early diagnosis of MBD.

Topics: Acid Phosphatase; Biomarkers; Collagen Type I; Diphosphonates; Humans; Imidazoles; Isoenzymes; Multiple Myeloma; Osteoporosis; Procollagen; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antibodies, Monoclonal, Humanized; Biomarkers; Bone Density Conservation Agents; Bone Diseases, Metabolic; Bone Resorption; Calcium; Cell Differentiation; Collagen Type I; Denosumab; Diphosphonates; Drug Substitution; Female; Humans; Imidazoles; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Myeloma Proteins; Osteoblasts; Osteocalcin; Osteogenesis; Peptides; RANK Ligand; Retrospective Studies; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

Skeletal homeostasis relies upon a fine tuning of osteoclast (OCL)-mediated bone resorption and osteoblast (OBL)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease (BD). Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells, significantly impairs tartrate acid phosphatase (TRAcP) expression, lacunae generation, and collagen degradation, which are relevant hallmarks of OCL activity. Accordingly, expression of cathepsin K and metalloproteinase 9 (MMP9) as well as actin ring rearrangement were impaired in the presence of miR-29b. Moreover, we found that canonical targets C-FOS and metalloproteinase 2 are suppressed by constitutive miR-29b expression which also downregulated the master OCL transcription factor, NAFTc-1. Overall, these data indicate that enforced expression of miR-29b impairs OCL differentiation and overcomes OCL activation triggered by MM cells, providing a rationale for miR-29b-based treatment of MM-related BD.

Topics: Acid Phosphatase; Actins; Bone Resorption; Cathepsin K; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Collagen Type I; Gene Expression; Genes, fos; Humans; Isoenzymes; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; MicroRNAs; Multiple Myeloma; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Osteolysis; Receptor Activator of Nuclear Factor-kappa B; Tartrate-Resistant Acid Phosphatase

To detect serum concentrations of Dickkopf-1 (DKK-1) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) in patients with multiple myeloma (MM) and to investigate its clinical significance.. Serum DKK-1, sRANKL, osteoprotegerin(OPG) and tartrate-resistant acid phosphatase 5b (TRACP-5b) levels were quantified in 30 newly diagnosed MM patients and 20 healthy control subjects by using sandwich ELISA.. The serum DKK-1, sRANKL, OPG and TRACP-5b levels were significantly higher than those in the healthy controls (42.96 µg/L vs 5.33 µg/L, 1.83 pmol/L vs 0.79 pmol/L, 1799.30 pmol/L vs 822.40 pmol/L, 5.81 U/L vs 0.28 U/L, respectively; all P < 0.05). Serum levels of DKK-1 were positively correlated with sRANKL and TRACP-5b, respectively. Serum concentrations of DKK-1 and sRANKL were significantly elevated in stage III vs stages I and II according to International Staging System (ISS) (46.33 µg/L vs 37.91 µg/L, 2.26 pmol/L vs 1.19 pmol/L, respectively, all P < 0.05). Serum concentrations of DKK-1, sRANKL and TRACP-5b were significantly higher in patients with more than 3 lytic bone lesions than those with only 1-3 lytic bone lesions (46.30 µg/L vs 31.98 µg/L, 2.18 pmol/L vs 0.69 pmol/L, 6.02 U/L vs 5.13 U/L, all P < 0.05).. MM patients have increased serum DKK-1, sRANKL, OPG and TRACP-5b levels as compared with the healthy controls. Serum concentrations of DKK-1 and sRANKL have close relationship with MM stage and lytic bone disease.

Topics: Acid Phosphatase; Adult; Aged; Carrier Proteins; Case-Control Studies; Female; Humans; Intercellular Signaling Peptides and Proteins; Isoenzymes; Male; Middle Aged; Multiple Myeloma; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Bone destruction is one of the most debilitating manifestations of multiple myeloma (MM) and results from the interaction of myeloma cells with the bone marrow microenvironment. Within the bone marrow, the disturbed balance between osteoclasts and osteoblasts is important for the development of lytic lesions. However, the mechanisms behind myeloma-mediated bone destruction are not completely understood. In order to address the importance of myeloma cell-osteoclast interactions in MM pathogenesis, we have developed a functional coculture system. We found that myeloma-osteoclast interactions resulted in stimulation of myeloma cell growth and osteoclastic activity through activation of major signalling pathways and upregulation of proteases. Signals from osteoclasts activated the p44/p42 MAPK, STAT3 and PI3K/Akt pathways in myeloma cells. In turn, myeloma cells triggered p38 MAPK and NF-kappaB signalling in osteoclasts. Myeloma-osteoclast interactions stimulated the production of TRAP, cathepsin K, matrix metalloproteinase (MMP)-1, -9, and urokinase plasminogen activator (uPA). Consistent data with myeloma cell lines and primary myeloma cells underlined the biological relevance of these findings. In conclusion, we demonstrated the critical role of myeloma cell-osteoclast interactions in the existing interdependence between tumour expansion and bone disease. The identified molecular events might provide the rationale for novel treatment strategies.

Topics: Acid Phosphatase; Bone Resorption; Cathepsin K; Cathepsins; Cell Communication; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Matrix Metalloproteinases; Multiple Myeloma; Osteoclasts; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured; Up-Regulation; Urokinase-Type Plasminogen Activator

A major clinical manifestation of bone cancers is bone destruction. It is widely accepted that this destruction is not caused by the malignant cells themselves, but by osteoclasts, multinucleated cells of monocytic origin that are considered to be the only cells able to degrade bone. The present study demonstrates that bone-resorbing osteoclasts from myeloma patients contain nuclei with translocated chromosomes of myeloma B-cell clone origin, in addition to nuclei without these translocations, by using combined FISH and immunohistochemistry on bone sections. These nuclei of malignant origin are transcriptionally active and appear fully integrated amongst the other nuclei. The contribution of malignant nuclei to the osteoclast population analysed in this study was greater than 30%. Osteoclast-myeloma clone hybrids contained more nuclei than normal osteoclasts and their occurrence correlated with the proximity of myeloma cells. Similar hybrid cells were generated in myeloma cell-osteoclast co-cultures, as revealed by tracing myeloma nuclei using translocations, bromo-deoxyuridine, or the Y chromosome of male myeloma cells in female osteoclasts. These observations indicate that hybrid cells can originate through fusion between myeloma cells and osteoclasts. In conclusion, malignant cells contribute significantly to the formation of bone-resorbing osteoclasts in multiple myeloma. Osteoclast-myeloma clone hybrids reflect a previously unrecognized mechanism of bone destruction in which malignant cells participate directly. The possibility that malignant cells corrupt host cells by the transfer of malignant DNA may have been underestimated to date in cancer research.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Bromodeoxyuridine; Cell Differentiation; Cell Nucleus; Clone Cells; Coculture Techniques; Female; Flow Cytometry; Humans; Hybrid Cells; Image Interpretation, Computer-Assisted; In Situ Hybridization, Fluorescence; In Situ Nick-End Labeling; Integrins; Interphase; Isoenzymes; Male; Microscopy, Fluorescence; Middle Aged; Multiple Myeloma; Osteoclasts; Receptors, Vitronectin; Syndecan-1; Tartrate-Resistant Acid Phosphatase; Translocation, Genetic

Osteolytic bone disease in multiple myeloma (MM) is associated with upregulation of osteoclast (OCL) activity and constitutive inhibition of osteoblast function. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway mediates OCL differentiation and maturation. We hypothesized that inhibition of ERK1/2 could prevent OCL differentiation and downregulate OCL function. It was found that AZD6244, a mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, blocked OCL differentiation and formation in a dose-dependent manner, evidenced by decreased alphaVbeta3-integrin expression and tartrate-resistant acid phosphatase positive (TRAP+) cells. Functional dentine disc cultures showed inhibition of OCL-induced bone resorption by AZD6244. Major MM growth and survival factors produced by OCLs including B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL), as well as macrophage inflammatory protein (MIP-1alpha), which mediates OCL differentiation and MM, were also significantly inhibited by AZD6244. In addition to ERK inhibition, NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1) and c-fos were both downregulated, suggesting that AZD6244 targets a later stage of OCL differentiation. These results indicate that AZD6244 inhibits OCL differentiation, formation and bone resorption, thereby abrogating paracrine MM cell survival in the bone marrow microenvironment. The present study therefore provides a preclinical rationale for the evaluation of AZD6244 as a potential new therapy for patients with MM.

Topics: Acid Phosphatase; Benzimidazoles; Biomarkers; Blotting, Western; Bone Resorption; Cell Differentiation; Chemokine CCL3; Chemokine CCL4; Cytokines; Depression, Chemical; Dose-Response Relationship, Drug; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression; Humans; Integrin alphaVbeta3; Isoenzymes; Macrophage Colony-Stimulating Factor; Macrophage Inflammatory Proteins; Mitogen-Activated Protein Kinases; Multiple Myeloma; Osteoclasts; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Transcription Factors; Tumor Cells, Cultured

B-cell-activating factor (BAFF) is a tumor necrosis factor superfamily member critical for the maintenance and homeostasis of normal B-cell development. It has been implicated in conferring a survival advantage to B-cell malignancies, including multiple myeloma (MM).. Here, we validate the role of BAFF in the in vivo pathogenesis of MM examining BAFF and its receptors in the context of patient MM cells and show activity of anti-BAFF antibody in a severe combined immunodeficient model of human MM.. Gene microarrays and flow cytometry studies showed increased transcripts and the presence of all three receptors for BAFF in CD138+ patient MM cells, as well as an increase in plasma BAFF levels in 51 MM patients. Functional studies show that recombinant BAFF protects MM cells against dexamethasone-induced apoptosis accompanied by an increase in survival proteins belonging to the BCL family. These in vitro studies led to the evaluation of a clinical grade-neutralizing antibody to BAFF in a severe combined immunodeficient human MM model. Anti-BAFF-treated animals showed decreased soluble human interleukin 6 receptor levels, a surrogate marker of viable tumor, suggesting direct anti-MM activity. This translated into a survival advantage of 16 days (P < 0.05), a decrease in tartrate-resistant acid phosphatase-positive osteoclasts, and a reduction in radiologically evident lytic lesions in anti-BAFF-treated animals.. Our data show a role for BAFF as a survival factor in MM. Importantly, the in vivo antitumor activity of neutralizing anti-BAFF antibody provide the preclinical rationale for its evaluation in the treatment of MM.

Topics: Acid Phosphatase; Animals; Antibodies; B-Cell Activating Factor; Cell Line, Tumor; Cell Survival; Gene Expression Profiling; Humans; Interleukin-6; Isoenzymes; Mice; Mice, SCID; Multiple Myeloma; Osteoclasts; Recombinant Proteins; Tartrate-Resistant Acid Phosphatase; Treatment Outcome

The effect of bortezomib on bone remodelling was evaluated in 34 relapsed myeloma patients. At baseline, patients had increased serum concentrations of dickkopf-1 (DKK-1), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of type-I collagen (CTX) and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b); bone-alkaline phosphatase and osteocalcin were reduced. Serum DKK-1 correlated with CTX and severe bone disease. Bortezomib administration significantly reduced serum DKK-1, sRANKL, CTX, and TRACP-5b after four cycles, and dramatically increased bone-alkaline phosphatase and osteocalcin, irrespective of treatment response. This is the first study showing that bortezomib reduces DKK-1 and RANKL serum levels, leading to the normalisation of bone remodelling in relapsed myeloma.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone Remodeling; Boronic Acids; Bortezomib; Case-Control Studies; Collagen Type I; Diphosphonates; Female; Humans; Imidazoles; Intercellular Signaling Peptides and Proteins; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Osteocalcin; Osteoprotegerin; Peptides; Protease Inhibitors; Pyrazines; RANK Ligand; Recurrence; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

Summary The ratio of osteoprotegerin [OPG, tumour necrosis factor receptor superfamily, member 11b (TNFRSF11B)] to receptor activator of nuclear factor kappaB ligand [RANKL, tumour necrosis factor (ligand) superfamily, member 11 (TNFSF11)] in bone is critical for the regulation of bone remodelling. Myeloma cells can home to bone, triggering increased RANKL and decreased OPG expression by stromal cells, leading to osteolysis. Whether myeloma cells contribute directly to the pool of RANKL or OPG in bone has been contentious. Here we provide evidence of RANKL expression by reverse transcription polymerase chain reaction and in situ hybridization, demonstrating transcripts encoding both the membrane-bound and secreted forms of RANKL in five human multiple myeloma cell lines (LP-1, NCI-H929, OPM-2, RPMI8226, U266) and myeloma cells purified from bone marrow aspirates of myeloma patients. We demonstrated that RANKL encoding mRNAs are translated to protein by antibody detection of RANKL. In vitro assays showed that myeloma cells induced bone marrow derived mononuclear cells to differentiate into adherent tartrate-resistant acid phosphatase positive multinucleated cells, indicative of the formation of functional osteoclasts. This differentiation could also be achieved with passaged myeloma media alone, implicating secreted products. Finally, we provide evidence that the differentiation observed is at least in part the result of myeloma cell expression of RANKL. We therefore conclude that myeloma cells can directly contribute to the pool of RANKL in bone.

Topics: Acid Phosphatase; Carrier Proteins; Cell Differentiation; Cell Division; Cell Line, Tumor; Culture Media, Conditioned; Gene Expression; Humans; In Situ Hybridization; Isoenzymes; Leukocytes, Mononuclear; Membrane Glycoproteins; Multiple Myeloma; Osteoclasts; Protein Isoforms; Proteoglycans; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Syndecans; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), a new marker reflecting osteoclast activity, and osteoprotegerin (OPG) were measured in 121 patients with multiple myeloma (MM) at diagnosis, and in 63 of them during pamidronate administration, to define their correlation with the extent of bone disease and disease activity in MM. Radiographic evaluation of the skeleton, measurement of other markers of bone remodelling, including N-terminal cross-linking telopeptide of type-I collagen (NTX), bone alkaline phosphatase and osteocalcin and of markers of disease activity (beta2-microglobulin, paraprotein, interleukin-6 (IL-6), were also performed. Levels of TRACP-5b were increased (p <.0001), while OPG was decreased in MM patients compared to controls (p <.01). TRACP-5b levels were associated with the radiographically assessed severity of bone disease (p <.0001) as well as with levels of NTX, IL-6 and beta2-microglobulin (p <.001, for each biochemical parameter, respectively). The combination of pamidronate with VAD-chemotherapy produced a reduction in TRACP-5b, NTX, IL-6, paraprotein and beta2-microglobulin levels from the 2nd month of treatment, with no effect on bone formation and OPG. A strong correlation was observed between changes in TRACP-5b and changes in NTX, IL-6 and beta2-microglobulin, while TRACP-5b predicted the disease progression in 5 patients. These findings suggest that TRACP-5b is increased in MM, reflects the extent of myeloma bone disease and may have a predictive value. TRACP-5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; C-Reactive Protein; Cytarabine; Dexamethasone; Diphosphonates; Female; Glycoproteins; Humans; Interleukin-6; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Osteocalcin; Osteoclasts; Osteogenesis; Osteoprotegerin; Pamidronate; Paraproteins; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reference Values; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase; Vincristine

Myeloma is a unique hematologic malignancy that exclusively homes in the bone marrow and induces massive osteoclastic bone destruction presumably by producing cytokines that promote the differentiation of the hematopoietic progenitors to osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow stromal cells influence the expression of the malignant phenotype in myeloma cells. This study examined the role of the interactions between myeloma cells and neighboring stromal cells in the production of osteoclastogenic factors to elucidate the mechanism underlying extensive osteoclastic bone destruction. A murine myeloma cell line 5TGM1, which causes severe osteolysis, expresses alpha(4)beta(1)-integrin and tightly adheres to the mouse marrow stromal cell line ST2, which expresses the vascular cell adhesion molecule-1 (VCAM-1), a ligand for alpha(4)beta(1)-integrin. Co-cultures of 5TGM1 with primary bone marrow cells generated tartrate-resistant acid phosphatase-positive multinucleated bone-resorbing osteoclasts. Co-cultures of 5TGM1 with ST2 showed increased production of bone-resorbing activity and neutralizing antibodies against VCAM-1 or alpha(4)beta(1)-integrin inhibited this. The 5TGM1 cells contacting recombinant VCAM-1 produced increased osteoclastogenic and bone-resorbing activity. The activity was not blocked by the neutralizing antibody to known osteoclastogenic cytokines including interleukin (IL)-1, IL-6, tumor necrosis factor, or parathyroid hormone-related peptide. These data suggest that myeloma cells are responsible for producing osteoclastogenic activity and that establishment of direct contact with marrow stromal cells via alpha(4)beta(1)-integrin/VCAM-1 increases the production of this activity by myeloma cells. They also suggest that the presence of stromal cells may provide a microenvironment that allows exclusive colonization of myeloma cells in the bone marrow. (Blood. 2000;96:1953-1960)

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Antigens, CD; Bone Marrow Cells; Bone Resorption; Cell Adhesion; Cell Communication; CHO Cells; Coculture Techniques; Cricetinae; Culture Media, Conditioned; Female; Gene Expression; Humans; Integrin alpha4; Integrin alpha4beta1; Integrins; Isoenzymes; Mice; Mice, Inbred C57BL; Multiple Myeloma; Neutralization Tests; Osteoclasts; Protein Binding; Rats; Receptors, Lymphocyte Homing; Recombinant Proteins; RNA, Messenger; Solubility; Stromal Cells; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured; Vascular Cell Adhesion Molecule-1

This study demonstrates that the multiple myeloma cell (MMC) in its plasma cell form is morphologically indistinguishable from human osteoclast-like cells that form in culture when peripheral blood mononuclear cells (PBMCs) are plated at high density in serum containing medium. MM has been described as a disease of B-cell lineage, monoclonal immunoglobulin (Ig) producing cells with unique properties: MM precursor cells lodge in bone, where they proliferate and differentiate into plasma cell tumors. Then, by some mechanism, presumably involving cytokines, these cells mediate an increase in neighboring osteoclast numbers and activity, leading to excessive bone erosion and hypercalcemia. Three days after plating PBMCs, tartrate resistant acid phosphatase- (TRAP-) blasts as well as TRAP+ cells, each with an eccentric nucleus, appear in culture. By day 10, TRAP+, vitronectin+ (VR+) cells, appear to be morphologically indistinguishable from multiple myeloma plasma cells (MMPCs) on cytocentrifuge preparations. These cells are CD19- and CD38++, as are MMCs reported by others. Other surface markers are also shared. Furthermore, Ig mRNA is demonstrated in the cytoplasm of cells at 8 days by in situ hybridization with the IgG FcA3 sequence. This novel finding is not unusual, in light of reports, demonstrating non-B-lineage Ig-producing cells. Thus, this study raises some serious questions about the true nature of MMCs.

Topics: Acid Phosphatase; ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Antigens, CD; Antigens, Differentiation; Antigens, Surface; Biomarkers; Cathepsin K; Cathepsins; Cells, Cultured; Female; Humans; Immunoglobulin G; Isoenzymes; Leukocytes, Mononuclear; Male; Membrane Glycoproteins; Middle Aged; Monocytes; Multiple Myeloma; NAD+ Nucleosidase; Naphthol AS D Esterase; Osteoclasts; Tartrate-Resistant Acid Phosphatase; Vitronectin

Enhanced bone resorption is a characteristic finding in multiple myeloma (MM). The aim of this study was to assess the newer biochemical bone markers in patients with myeloma. We studied 17 MM patients--10 males (3 untreated, 5 in remission, 2 responding), 7 females (3 in remission, 4 responding) and 15 normal controls. Serum bone specific alkaline phosphatase (BSALP), osteocalcin (OC) and procollagen type 1 C-terminal peptide (PICP) were determined as markers of bone formation, while serum tartrate resistant acid phosphatase (TRAP), urinary deoxypyridinoline (Dpyr) and calcium (Ca) were determined as markers of bone resorption and the ratio of the levels of bone formation/resorption were determined. All markers were measured by enzyme immunoassays (Metra Biosystems), except for TRAP by an in-house enzymatic assay and Ca by the cresolphthalein method. The Dpyr and Ca were expressed as a ratio to urinary creatinine (Cr) excretion. There were significantly higher (i) (Dpyr/Cr)/PICP ratio in male MM patients than in controls (P < 0.05); (ii) (a) urinary Dpyr excretion (P < 0.001), (b) (Dpyr/Cr)/BSALP ratio (P < 0.0001) and (c) (Dpyr/Cr)/PICP (P < 0.0001) in the untreated male MM subgroup than controls; (iii) (Dpyr/Cr)/BSALP ratio (P < 0.05) in the untreated than in the responding male MM subgroup, (iv) (Dpyr/Cr)/PICP ratio (P < 0.05) in untreated male patients than in those in the remission subgroup. In conclusion, (a) Dpyr is a sensitive marker in assessment of bone resorption in MM patients; (b) (Dpyr/Cr)/BSALP or (Dpyr/Cr)/PICP ratio is even more sensitive in distinguishing the untreated from the other MM subgroups and controls. Therefore, the use of a combination of these markers may have a potential role in the management of patients with MM.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers, Tumor; Bone and Bones; Bone Resorption; Calcium; Creatinine; Female; Humans; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Osteocalcin; Peptide Fragments; Procollagen; Sex Factors; Tartrate-Resistant Acid Phosphatase

The clinical significance of plasma cell acid phosphatase (PCAP) was evaluated in 143 patients with monoclonal gammapathies, using a semiquantitative cytological scoring method. Significantly higher PCAP scores were measured in overt myelomas than in MGUS or in smouldering myelomas, during the phases of activity (diagnosis, progression, relapse), and in patients with extended disease. Among various clinical and laboratory parameters, PCAP was significantly related to the percentage of bone marrow plasma cells, the neoplastic growth fraction, as determined by Ki67 monoclonal antibody, and to serum levels of C-reactive protein. An inverse relationship was also found between PCAP and hemoglobin levels. Although the patients with "flaming" plasma cells exhibited low PCAP scores and poor prognosis, on the whole, myeloma patients with PCAP scores < 200 showed a significantly longer median overall survival than those with PCAP > 200 (46 vs 20 months, p < 0.003). However, in the multivariate analysis, beta 2-microglobulin, growth fraction, performance status, and serum levels of thymidine kinase and C-reactive protein, but not PCAP, maintained a significant prognostic relevance. In conclusion, although PCAP may be considered a marker of disease activity, other parameters provide better prognostic information in myeloma patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Multiple Myeloma; Plasma Cells; Prognosis

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Multiple Myeloma; Plasma Cells; Prognosis

Increased bone resorption in the vicinity of myeloma cells is mediated by local stimulating factors. Other malignancies of the B cell lineage are also able to produce resorbing factors responsible for increased bone resorption. We have studied three groups of subjects: 10 patients with overt multiple myeloma, 10 patients with a B cell malignancy, and 10 healthy human subjects as controls. Patients were studied at the time of diagnosis and had a transiliac bone biopsy. Osteoclasts were evident on histological sections by their acid phosphatase activity. A software was developed on an automatic image analyzer (Leitz TAS+) for measuring the maximal Feret's diameter (Oc.Le) of each osteoclast (corresponding to the osteoclast length). The histogram of Oc.Le frequency distribution was supplied in each group. In myeloma patients, the Oc.Le frequency distribution was similar to that in normal subjects and showed the histogram to be asymetric with a positive skew (maximum peak at 20-25 microns). With a graphical analysis, this distribution was shown to follow a lognormal distribution corresponding to a homogeneous osteoclast population. In other B cell malignancies, Oc.Le displayed a bimodal distribution with a peak at 20-25 microns and a lower peak at 10-15 microns. The graphical analysis showed that small (mononucleated?) osteoclasts are present in B cell malignancies with normal osteoclasts. This might reflect the secretion of different soluble factors by malignant cells of the B lymphocyte lineage.

Topics: Acid Phosphatase; B-Lymphocytes; Biopsy; Bone and Bones; Bone Neoplasms; Humans; Multiple Myeloma; Osteoclasts; Software; Staining and Labeling

In two cases of vacuolated plasma cells, one of which was associated with primary macroglobulinemia and the other was with kappa-chain Bence Jones multiple myeloma, we examined the immunopathological features of the vacuoles in order to know whether the Ig-secreting system or the lysosomal system is of importance in the process of vacuole formation. Immunofluorescent studies detected no Ig in the vacuoles. Detection of intracellular Ig by immunoelectron microscopic technique revealed that Ig was localized only in a small portion of the vacuoles but not in most vacuoles. Even when Ig was included in the vacuoles, only the contents of the vacuoles were positive for Ig but their demarcating membrane was negative for Ig. In contrast, electron microscopic studies of acid phosphatase activity revealed the presence of its activity in all vacuoles. These findings suggest that the lysosomal system but not the Ig-secreting system may play a major role in vacuolation of these myeloma cells.

Topics: Acid Phosphatase; Bence Jones Protein; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoglobulin kappa-Chains; Immunoglobulins; Male; Microscopy, Electron; Middle Aged; Multiple Myeloma; Plasma Cells; Vacuoles; Waldenstrom Macroglobulinemia

Practically all myeloma cells had prominent vacuoles, around and within which the end product of acid phosphatase (AP) reaction was demonstrated. These vacuoles were considered to be autophagic. In remission, only a few myeloma cells were vacuolated. Serial determinations showed transition from an initial high AP score (3.86) to a low score (1.32) in remission. Moreover, there was a trend towards a lower average percentage of positive cells in remission (72%) as compared to the preinduction phase (100%). Intracellular Bence Jones proteins of the present case may be toxic and capable of causing vacuolation with activation of lysosomal enzymes.

Topics: Acid Phosphatase; Bone Marrow; Bone Marrow Cells; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Multiple Myeloma; Plasma Cells

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; Immunoglobulins; Male; Middle Aged; Multiple Myeloma; Plasma Cells

Monoclonal antibodies against human prostatic acid phosphatase (PAPase) were produced by immunization of human primary spleen cell cultures. Dissociated spleen cells were cultured for 5-8 days in the presence of 100 ng/ml of PAPase and pokeweed mitogen (1:5000). Following immunization, B cells were isolated and infected with Epstein-Barr virus (EBV). Two weeks after EBV-transformation, cells were fused with either mouse myeloma cells (SP2/OAg14) or human/mouse heteromyeloma cells (SHM-D33). Hybrid clones were screened for anti-PAPase production. In 7 independent immunizations, the average fusion frequency was 3.6 per 10(6) lymphocytes. 18-32% of the hybridomas produced anti-PAPase; approximately 75% of these secreted IgM and 25% secreted IgG. Antibody specificity was determined by immunoassay and immunohistological studies. The procedures described here may be suitable for the production of human monoclonal antibody of a useful specificity.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Antibody Specificity; B-Lymphocytes; Cell Fusion; Herpesvirus 4, Human; Humans; Hybridomas; Immunoenzyme Techniques; Male; Mice; Multiple Myeloma; Pokeweed Mitogens; Prostatic Hyperplasia; Spleen

The differential diagnostic significance of acid phosphatase and beta-glucuronidase were studied in 77 cases of low-grade B cell non-Hodgkin's lymphomas. In most cases the results of cytochemical enzyme studies performed on malignant cells of the bone marrow were evaluated. B cell chronic lymphocytic leukaemia, centrocytic and centroblastic/centrocytic lymphomas were characterized by a weak or a negative acid phosphatase and beta-glucuronidase activity. Stronger positivity was observed in immunocytoma and in Waldenström's macroglobulinaemia, while the highest activity was found in multiple myeloma. Hairy cell leukaemia of B cell origin showed intensive tartrate-resistant acid phosphatase activity. The cytochemical examination of these lysosomal enzymes may be useful in the diagnosis of low-grade malignant lymphomas of B cell origin by completing other methods.

Topics: Acid Phosphatase; Adult; B-Lymphocytes; Bone Marrow; Glucuronidase; Humans; Leukemia, Hairy Cell; Leukemia, Lymphoid; Lymphoma; Lymphoma, Follicular; Lysosomes; Multiple Myeloma; Waldenstrom Macroglobulinemia

A detailed classification of plasma cells stained for acid phosphatase activity is introduced. With this method, patients with multiple myeloma, non-myeloma gammopathies, reactive plasmacytosis and other diseases in which plasma cells are involved, were investigated. The results show that our method can discriminate between multiple myeloma and reactive plasmacytosis. The overlap between multiple myeloma and other monoclonal gammopathies is much smaller than observed in other studies. Surprisingly low levels of acid phosphatase activity were found in the cells from patients with lymphoplasmacytoid immunocytoma. It is concluded that the acid phosphatase score can be of value for studying disorders in which plasma cells are involved.

Topics: Acid Phosphatase; Histocytochemistry; Humans; Leukemia, Plasma Cell; Lymphoma; Lymphoproliferative Disorders; Multiple Myeloma; Plasma Cells

Topics: Acid Phosphatase; Bone Marrow; Diagnosis, Differential; Humans; Hypergammaglobulinemia; Multiple Myeloma; Naphthol AS D Esterase; Plasma Cells; Waldenstrom Macroglobulinemia

Acid phosphatase activity was studied cytochemically in bone marrow plasma cells of 32 multiple myelomas, 45 non-myelomatous monoclonal gammopathies and 20 normal subjects. We have found significant differences among these three groups (P less than 0.001). The usefulness of this cytochemical reaction for the study of monoclonal gammopathies is discussed.

Topics: Acid Phosphatase; Aged; Bone Marrow; Clinical Enzyme Tests; Diagnosis, Differential; Hemoglobins; Humans; Hypergammaglobulinemia; Leukocyte Count; Middle Aged; Multiple Myeloma; Plasma Cells

The activity of acid phosphatase in bone marrow plasma cells was investigated by a cytochemical method in 12 patients with multiple myeloma, in 12 patients with benign monoclonal gammopathy and in 5 normal controls. The activity of acid phosphatase was significantly higher in the multiple myeloma patients compared with the activity observed in controls and in benign monoclonal gammopathy patients (p less than 0.001). It is therefore suggested that this method may be a valuable adjunct in the differential diagnosis of monoclonal immunoglobulinemias .

Topics: Acid Phosphatase; Adult; Aged; Bone Marrow Examination; Diagnosis, Differential; Female; Histocytochemistry; Humans; Hypergammaglobulinemia; Male; Middle Aged; Multiple Myeloma; Neoplasm Staging; Plasma Cells

Three plasma cell enzymatic reactions--ATPase, acid phosphatase (AP), alpha-naphthyl acetate esterase (alpha-NAE)--were tested in a large number of bone marrow samples from patients with multiple myeloma (MM), benign monoclonal gammapathy (BMG)--idiopathic (iBMG) and secondary (sBMG)--, polyclonal hypergammaglobulinemia (PH), Waldenström's macroglobulinemia (WM) and from normoglobulinemic subjects (NS). The purpose of the present study was to evaluate the significance of these reactions in differential diagnosis of BMG and initial or atypical MM. For each reaction results were expressed as scores and normal limits were statistically established. Our findings in MM, HP and NS are consistent with previous reports (similar enzymatic pattern in NS and PH; depressed ATPase activity, raised AP and alpha-NAE activities in most MM cases). In the BMG class, ATPase activity was normal in about 40% of iBMG, while it was depressed in other cases; most sBMG had diminished ATPase activity. AP patterns were normal for both BMG groups. alpha-NAE activity was normal in 50% of iBMG, while it was raised in the other cases. All the reactions were normal in WM. In a bayesian analysis of cytochemical patterns of NS and MM subjects ATPase showed the highest diagnostic significance, followed by alpha-NAE and AP. ATPase, therefore, seems to be the most useful criterion for the diagnosis of initial MM; low ATPase score BMG patients should therefore be carefully followed-up.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Bone Marrow; Clinical Enzyme Tests; Diagnosis, Differential; Humans; Hypergammaglobulinemia; Multiple Myeloma; Naphthol AS D Esterase; Plasma Cells

Acid phosphatase (AcP) in neoplastic cells from various lymphoid leukemias was examined. In the cytochemical studies, tartrate-resistant AcP (T-rAcP) activity was observed in the neoplastic cells from well-differentiated lymphoid leukemias such as adult T-cell leukemia (ATL), B-cell chronic lymphocytic leukemia (B-CLL), T-cell chronic lymphocytic leukemia (T-CLL), and hairy-cell leukemia (HCL). T-rAcP activity was also detected in a small number of leukemic cells obtained from T-cell acute lymphoblastic leukemia (T-ALL), while it was not detected in the neoplastic cells from null-ALL, macroglobulinemia, and multiple myeloma (MM). In the electrophoretical studies, fraction 1 (F-1), F-3, F-3b, and F-4 were completely tartrate-sensitive, while F-2 was partially resistant and F-5 was completely resistant. T-rAcP activity (F-5) was observed in ATL cells, B-CLL cells, and HCL cells, while it was not detected in ALL cells, macroglobulinemia cells, and MM cells. The present study indicates that T-rAcP activity is observed not only in HCL cells but also in the well-differentiated lymphoid cells such as ATL cells, B-CLL and T-CLL cells except the most highly differentiated forms of B-cells of MM and macroglobulinemia.

Topics: Acid Phosphatase; Cell Transformation, Neoplastic; Electrophoresis, Polyacrylamide Gel; Humans; Isoenzymes; Leukemia, Hairy Cell; Leukemia, Lymphoid; Multiple Myeloma; T-Lymphocytes; Tartrates; Waldenstrom Macroglobulinemia

Plasma cell acid phosphatase has been studied in 51 patients, 30 of whom were affected with multiple myeloma (MM) and 21 with nonmyelomatous monoclonal immunoglobulinemias (NMMI). Scoring of results displayed a highly significant difference between the median of the MM and NMMI group (343 vs. 204). The use of plasma cell acid phosphatase as a further criterion in the differential diagnosis of monoclonal immunoglobulinemiasis emphasized.

Topics: Acid Phosphatase; Clinical Enzyme Tests; Diagnosis, Differential; Humans; Hypergammaglobulinemia; Multiple Myeloma; Plasma Cells

The acid phosphatase activity has been studied cytochemically in bone marrow plasma cells of 12 patients with multiple myeloma and 15 with non-myeloma plasmocytosis. The acid phosphatase activity has been significantly higher in the myeloma group. The utilization and usefulness of this cytochemical reaction for the diagnosis of multiple myeloma are proposed.

Topics: Acid Phosphatase; Aged; Bone Marrow Cells; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; Hypergammaglobulinemia; Immunoglobulin A; Male; Middle Aged; Multiple Myeloma; Plasma Cells

Acid phosphatase (AP) activity of plasma cells was studied in 38 patients with multiple myeloma (MM). The average activity per cell was strong (mean score = 2.42; maximum score = 4) and the percentage of positive cells was greater than 90% in over 71% of patients. The average AP activity per cell was higher prior to treatment (3.06 +/- 0.53) compared to relapse (2.48 +/- 0.77) and remission (1.81 +/- 1.02 (p less than 0.05 and p less than 0.01, respectively). In correlation of AP activity with clinical features at the time of the study, the only significant difference was between kappa and lambda subtype. Patients with lambda MM had a higher average AP activity per cell in remission (2.71 +/- 0.43) as opposed to kappa MM (1.17 +/- 1.06, p less than 0.05 for difference). AP activity was not significantly correlated with degree of bone involvement. However, activity seemed to be a good marker of disease activity.

Topics: Acid Phosphatase; Aged; Aging; Bone Marrow; Calcium; Female; Hemoglobins; Humans; Immunoglobulin Light Chains; Immunoglobulins; Male; Middle Aged; Multiple Myeloma; Plasma Cells; Remission, Spontaneous

Peripheral blood smears and bone-marrow smears from 29 patients with malignant M-components (25 with multiple myeloma and 4 with malignant lymphoma), 13 patients with benign monoclonal gammopathy (BMG), and 20 patients with polyclonal reactive plasmacytosis were examined by leucocyte alkaline phosphatase score (LAP-score) and by acid phosphatase score in plasma cells from bone-marrow smears. Furthermore, tissue sections from marrow biopsies from all patients were examined by the three-layer unlabelled immunoperoxidase technique to detect cytoplasmic immunoglobulin. The LAP-score was significantly higher in patients with malignant M-components than in patients with BMG and also higher in IgA and IgG myeloma than in IgA and IgG BMG, but the latter difference was not significant. Furthermore, a significant positive correlation between paraprotein concentration and LAP-score was found in multiple myeloma. Acid phosphatase score in plasma cells showed no clear distinction between multiple myeloma and BMG. Immunohistochemical examination showed a distinct monoclonal pattern in both multiple myeloma and BMG, allowing identification of the M-component which in all cases corresponded to the M-component detected by serum examination. Cells producing immunoglobulin classes not matching the M-component were more rare in multiple myeloma than in BMG, but the difference between the two conditions was quantitative and allowed no clear distinction.

Topics: Acid Phosphatase; Bone Marrow; Humans; Hypergammaglobulinemia; Immunoenzyme Techniques; Immunoglobulins; Lymphocytes; Lymphoma; Multiple Myeloma; Plasmacytoma

Topics: Acid Phosphatase; Adenosine Triphosphatases; Blood Protein Disorders; Esterases; Humans; Multiple Myeloma; Plasma Cells; Plasmacytoma; Waldenstrom Macroglobulinemia

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adult; Aged; Esterases; Female; Humans; Male; Middle Aged; Multiple Myeloma; Plasma Cells; Plasmacytoma

Acid phosphatase activity estimated cytochemically is markedly increased in myeloma plasma cells compared to that found in normal plasma cells, polyclonal plasma-cytoses and most interestingly in the non-myelomatous monoclonal dysglobulinaemias. In the differential diagnosis of this last group the test has a useful role.

Topics: Acid Phosphatase; Aged; Diagnosis, Differential; Dysgammaglobulinemia; Humans; Multiple Myeloma; Plasma Cells

Prostatic acid phosphatase and alkaline phosphatase values in bone marrow were correlated with skeletal surveys and diagnoses during a six-month study. In cases of biopsy-proven adenocarcinoma of the prostate, bone marrow prostatic acid phosphatase was the most consistently abnormal value. Diagnoses other than prostatic cancer involving the bone marrow, e.g., myeloma and leukemias, were associated with elevated prostatic acid phosphatase and alkaline phosphatase values. In cases in which the bone marrow was not involved by metastasis, these values were normal. Bone marrow prostatic acid phosphatase assay was found to be a very good tool for detecting early osseous metastases from any site, including prostatic adenocarcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Bone Marrow; Bone Neoplasms; Humans; Leukemia; Male; Multiple Myeloma; Neoplasm Metastasis; Prostatic Neoplasms

26 cases of malignant lymphomas and 23 other lymphoreticular conditions were investigated enzyme histochemically. Each type of malignant lymphoma revealed a different enzyme histochemical pattern characteristic of its type. These features are not only applicable to differential diagnosis but also suggest clues to the understanding of histogenesis and nature of malignant lymphomas.

Topics: Acid Phosphatase; Esterases; Glucuronidase; Histocytochemistry; Hodgkin Disease; Humans; Hyperplasia; Isoenzymes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Naphthols

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Bone Neoplasms; Carcinoma; Esterases; Glucuronidase; Histocytochemistry; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Monoamine Oxidase; Multiple Myeloma; Neoplasm Metastasis; Neuroblastoma; Plasmacytoma; Sarcoma, Ewing

Topics: Acetylcholinesterase; Acid Phosphatase; Cholinesterases; Electrophoresis, Polyacrylamide Gel; Esterases; Humans; L-Lactate Dehydrogenase; Multiple Myeloma; Proteinuria; Ribonucleases

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Female; Hematologic Diseases; Humans; Injections, Intravenous; Male; Middle Aged; Movement; Multiple Myeloma; Neoplasm Metastasis; Pain, Intractable; Radionuclide Imaging; Remission, Spontaneous; Strontium Radioisotopes; Urinary Bladder Neoplasms; Uterine Neoplasms

Topics: Acid Phosphatase; Blood Proteins; Diagnosis, Differential; Esterases; Histocytochemistry; Humans; Microscopy, Electron; Multiple Myeloma; Naphthacenes; Naphthols; Neoplasm Proteins; Plasmacytoma; Staining and Labeling

Topics: Acid Phosphatase; Alkaline Phosphatase; Esterases; Glucuronidase; Histocytochemistry; Hodgkin Disease; Humans; L-Lactate Dehydrogenase; Lectins; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Peroxidases; Sarcoma

Topics: Acid Phosphatase; Animals; Antibody Specificity; Antibody-Producing Cells; Cattle; Cell Line; Cyclic AMP; Immune Sera; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin Fragments; Immunoglobulin M; Leucine; Mice; Microscopy, Phase-Contrast; Mitosis; Multiple Myeloma; Phagocytosis; Rabbits; Thymidine; Tritium; Trypsin; Trypsin Inhibitors

Topics: Acid Phosphatase; Acute Disease; Adenosine Triphosphatases; Alkaline Phosphatase; Asparaginase; Bone Marrow; Bone Marrow Cells; Carcinoma; Depression, Chemical; Esterases; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Lupus Erythematosus, Discoid; Lymphatic Diseases; Multiple Myeloma; Peroxidases; Stimulation, Chemical

Topics: Acid Phosphatase; Adenosine Triphosphatases; Bone Marrow; Esterases; Histocytochemistry; Humans; Multiple Myeloma; Plasma Cells; Waldenstrom Macroglobulinemia

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphoma; Male; Middle Aged; Multiple Myeloma; Muramidase; Sarcoidosis; Seasons

Topics: Acid Phosphatase; Adenosine Triphosphatases; Aged; Alkaline Phosphatase; Autopsy; Blood Proteins; Bone Marrow Cells; Bone Marrow Examination; Diagnosis, Differential; Esterases; Histocytochemistry; Humans; Immunoelectrophoresis; Lymphocytes; Male; Microscopy, Electron; Mitochondria; Multiple Myeloma; Naphthaleneacetic Acids; Peroxidases; Plasma Cells; Ultracentrifugation; Waldenstrom Macroglobulinemia

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Proteins; Bone Marrow; Bone Marrow Cells; Female; Glucosephosphate Dehydrogenase; Glycoproteins; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Male; Multiple Myeloma; Periodic Acid; Plasma Cells; Succinate Dehydrogenase; Waldenstrom Macroglobulinemia

Topics: Acid Phosphatase; Alkaline Phosphatase; Anemia, Aplastic; Bone Marrow; Disease; Hemochromatosis; Histocytochemistry; Humans; Hypersplenism; Leukocyte Count; Lymphatic Diseases; Methods; Mononuclear Phagocyte System; Multiple Myeloma; Neutrophils; Staining and Labeling

Topics: Acid Phosphatase; Adult; Aged; Azo Compounds; Bence Jones Protein; gamma-Globulins; Histocytochemistry; Humans; Immunoglobulin G; Male; Microscopy, Electron; Middle Aged; Multiple Myeloma

Topics: Acid Phosphatase; Electrophoresis, Disc; Female; Gaucher Disease; Hot Temperature; Humans; Isoenzymes; Liver; Lymph Nodes; Male; Multiple Myeloma; Prostate; Prostatic Neoplasms; Spleen

Topics: Acid Phosphatase; Bence Jones Protein; Beta-Globulins; Bone Marrow; Bone Marrow Cells; Esterases; Golgi Apparatus; Histocytochemistry; Humans; Lysosomes; Mitochondria; Multiple Myeloma

Topics: Acid Phosphatase; Alkaline Phosphatase; Autoradiography; DNA; Electron Transport Complex IV; Histocytochemistry; Humans; In Vitro Techniques; Lipids; Multiple Myeloma; Nucleosides; Peroxidases; Phospholipids; Plasma Cells; Polysaccharides; Proteins; RNA; Thymidine; Tritium; Uridine

Topics: Acid Phosphatase; Densitometry; Electrophoresis; Female; Gaucher Disease; Humans; Isoenzymes; Male; Multiple Myeloma; Prostatic Neoplasms

Topics: Acid Phosphatase; Anemia; Anemia, Aplastic; Azo Compounds; Blood Cells; Bone Marrow Cells; Histocytochemistry; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Mycosis Fungoides; Neoplasms; Polycythemia Vera; Sarcoma