muramidase and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

We report on two patients with chronic myeloid leukemia (CML) who presented blastic transformation involving the skin, with leukemic infiltrates showing unusual morphologic and immunohistologic characteristics. Both patients were elderly men with a 36-month and a 40-month history of CML, respectively. They presented with disseminated, reddish to violaceous papules and plaques (case 1), and with localized reddish nodules on the left temporal area (case 2). Concurrent features of blastic transformation in the bone marrow were observed in one patient (case 1). Histopathologic examination of skin lesions revealed similar features in both cases. There was a moderate to dense dermal infiltrate composed mainly of medium-sized atypical mononuclear myeloid precursor cells with only few relatively well-differentiated cells of the granulocytic series. Histochemical staining for naphthol-ASD-chloroacetate esterase revealed strong positivity (>50% of neoplastic cells) in case 2 and only scattered positivity (< 10% of neoplastic cells) in case 1. Immunohistologic analysis performed on paraffin-embedded sections showed in both cases variable reactivity of neoplastic cells for leucocyte common antigen (CD45), lysozyme, myeloperoxidase, CD11c, CD15, CD43, CD66, CD68, HLA-DR, and the neural cell adhesion molecule (NCAM) CD56. A negative reaction was observed for CD3, CD34, and TdT. The immunohistologic findings were remarkably similar to those reported for acute myeloid leukemia (AML) with monocytic differentiation (French-American-British [FAB] classification, subtype M4). Examination of blasts from the bone marrow performed in one patient (case 1) revealed a similar phenotype also with CD56 expression. In conclusion, our observations show that specific cutaneous infiltrates in CML may show morphologic and immunohistochemical characteristics similar to those observed in AML with monocytic differentiation. Moreover, specific cutaneous manifestations of CML may express CD56.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Marrow Cells; CD56 Antigen; HLA-DR Antigens; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemic Infiltration; Lymphocyte Activation; Male; Middle Aged; Muramidase; Naphthol AS D Esterase; Peroxidase; Skin Neoplasms; T-Lymphocytes

The occurrence of opportunistic pathogens and the concentration of some antimicrobial factors in the oral cavity of both acute and chronic leukaemia patients were studied. Enterobacteria were isolated from both dental plaque and crevicular fluid of all the groups examined, with few differences between healthy volunteers and leukaemic subjects; yeasts were found in both the crevicular fluid and the dental plaque samples of chronic leukaemia patients, but only in the plaque of healthy volunteers. Acute leukaemia patients did not have yeasts, but they were the only group colonized by the pseudomonads. IgA and N-acetyl-D-glucosaminidase (NAGase) significantly increased in chronic leukaemia patients compared with controls, whilst lysozyme seemed to present no marked differences for all groups. A further increase in NAGase concentration and an elevation in lysozyme content of saliva was observed for chronic leukaemia patients with severe periodontal lesions.

Topics: Acetylglucosaminidase; Dental Plaque; Enterobacteriaceae; Gingival Crevicular Fluid; Humans; Immunoglobulin A; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Mouth; Muramidase; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas; Saliva; Yeasts

Chronic granulocytic leukemia is a rare myeloproliferative disorder in dogs. The present study investigated various functions of leukemic granulocytes in a dog that presented with thrombocytopenic purpura, anaemia and a classical leukemic hemogram. All analyses were performed in parallel with a control dog. Purification of the leukemic granulocytes by density gradient centrifugation revealed three neutrophil and neutrophil precursor populations with different densities. Comparison of cell morphology and density showed that cell density increased with increasing maturity. The control dog possessed only one neutrophil population, with a density greater than 1.077. Analysis of cellular contents of the granular enzymes, elastase, myeloperoxidase and lysozyme showed that leukemic neutrophils were quantitatively markedly different from normal neutrophils with respect to enzyme activities. There were no major differences between leukemic and normal cells as regards aggregatory and migratory responses to different stimuli. The phagocytic capacity of the leukemic cells, however, was dramatically increased compared with the control, and exceeded all previously encountered responses in the assay employed. In a similar fashion, superoxide generation and secretion of elastase and lysozyme in response to zymosan and phorbol myristate acetate were substantially higher than in the control dog. Priming of cell function to a level exceeding that normally attainable in neutrophils appears to have taken place in peripheral blood of the leukemic dog. The only endogenous mediator known to prime neutrophil functions to the extent seen in the present case is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is intimately involved in regulation of myelopoiesis in mammals. On the basis of the enzymological and functional findings in the leukemic dog, we hypothesize that a lactoferrin deficiency in leukemic neutrophils leads to enhanced GM-CSF synthesis, which is ultimately the cause of the observed cellular hyperresponsiveness and contributes to the monocytosis seen in the patient.

Topics: Animals; Cell Aggregation; Cell Separation; Centrifugation, Density Gradient; Chemotaxis, Leukocyte; Dog Diseases; Dogs; Female; Granulocytes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Muramidase; Pancreatic Elastase; Peroxidase; Phagocytosis; Superoxides

The features of nonspecific defense factors were studied in 42 patients with chronic myeloid leukemia (CML) and in 18--with chronic subleukemic myelosis (CSM), in the presence of the treatment including polychemotherapy and plasmocytapheresis. Significant changes have been detected in the humoral factors of nonspecific defense (lysozyme, beta-lysins, complement components), as well as in the cellular component (phagocytic activity of the cells) in CML patients, these changes were growing with the leukemic process progressing. Plasmocytapheresis conducted produced no appreciable effect on the parameters of nonspecific resistance in the patients.

Topics: Antimicrobial Cationic Peptides; Blood Proteins; Complement System Proteins; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Monocytes; Muramidase; Neutrophils; Phagocytosis; Primary Myelofibrosis; Proteins

In this study immuno-electron microscopy was used to assay, semi-quantitatively, the granule contents of elastase, lactoferrin, lysozyme and myeloperoxidase in human peripheral blood neutrophils from 13 chronic myeloid leukaemia patients in the chronic phase of the disease and from normal non-smoking donors. The fixation conditions that adequately preserved the antibody binding capacities of these antigens and reasonably preserved the ultrastructure of the neutrophils were selected by light-microscopic immunoperoxidase cytochemistry on cytospin smears. Immunogold cytochemistry on LR White resin sections localised elastase and myeloperoxidase to the primary granules, lactoferrin to the secondary granules and lysozyme to both types of granule. When applicable, peroxidase cytochemistry was combined with immunogold staining making it easier to distinguish the primary from the secondary granules. A comparison of the immunolabelling density values obtained for the leukaemic and normal states revealed no significant abnormalities in the immunoreactivity patterns for any of these neutrophil granule antigens in the leukaemic patients. All 13 patients gave normal immunostaining reactivities for these neutrophil granule proteins. Consequently the distribution patterns of these proteins, as shown in this study, cannot be used as indices in distinguishing chronic myeloid leukaemic neutrophils from normal neutrophils.

Topics: Adult; Blood Proteins; Cytoplasmic Granules; Female; Humans; Immunohistochemistry; Lactoferrin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Microscopy, Electron; Muramidase; Neoplasm Proteins; Neutrophils; Pancreatic Elastase; Peroxidase

After exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA), cells of the promyelocytic leukemia cell line, HL-60, differentiate into macrophage-like cells. Within 24 h the cells adhere to the surface of the culture flask and increase production of nonspecific esterases. The intracellular concentration of the serine proteases increases two- to threefold within 4 days and continues to increase as the cells develop into mature macrophages. The acid hydrolases, lysozyme and beta-glucuronidase, were secreted by the differentiated cells. Both the intracellular and extracellular concentrations of these enzymes continued to increase as the cells matured. The fully differentiated cells readily phagocytized opsonized yeast cells. Phagocytosis had little effect on the secretion of acid hydrolases, while intracellular proteases increased significantly. The fully differentiated HL-60 cells resembled normal macrophages regarding all parameters studied. Viability of the differentiated cells exceeded 50% when cultured for 30 days. Therefore, these cells should prove to be a useful tool for the study of macrophage function with respect to microorganisms that are resistant to destruction by phagocytic cells.

Topics: Candida albicans; Cell Differentiation; Cell Line; Chymotrypsin; Glucuronidase; Humans; Hydrolases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Muramidase; Pancreatic Elastase; Phagocytosis; Serine Endopeptidases; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured