lewis-x-antigen and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

To explore the possible molecular mechanism of Ikaros regulation on FUT4 expression by analyzing the correlation of the functional state of Ikaros with level of FUT4 expression, so as to provide the theoretical basis for personalized treatment in children with ALL.. The subtypes of Ikaros were identified by nested PCR and sequencing. The expression level of FUT4 was detected by quantitative PCR and analyzed by ΔΔCt method in the early stage of treatment, remission and relapse of ALL.. Ik1 and Ik2 were the main functional subtypes, and the dominant negative Ikaros was Ik6; the Ik6 was detected in 23 patients with ALL. It was found that 2.73% patients expressing Ik6 alone and 18.18% patients with heterozygous expression were detected. The expression of FUT4 in the newly diagnosed ALL was higher than that in the control group, and the functional Ikaros negatively correlated with the FUT4 expression(r=-0.6329).. Dominant negative Ikaros closely correlated with the relapse of acute lymphoblastic leukemia in children. The functional Ikaros negatively correlated with FUT4 expression. Ikaros inhibit the transcriptional activity of FUT4, that may be the molecular mechanism of Ikaros regulating the expression of FUT4.

Topics: Acute Disease; Child; Fucosyltransferases; Humans; Ikaros Transcription Factor; Lewis X Antigen; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Isoforms; Recurrence

The MLL-AF9 fusion gene is associated with aggressive leukemias of both the myeloid and lymphoid lineage in infants, whereas in adults, this translocation is mainly associated with acute myeloid leukemia. These observations suggest that differences exist between fetal and adult tissues in terms of the 'cell of origin' from which the leukemia develops. Here we show that depending on extrinsic cues, human neonatal CD34(+) cells are readily immortalized along either the myeloid or lymphoid lineage upon MLL-AF9 expression and give rise to mainly lymphoid leukemia in immunocompromised mice. In contrast, immortalization of adult bone marrow CD34(+) cells is more difficult to achieve and is myeloid-biased, even when MLL-AF9 is expressed in purified hematopoietic stem cells (HSCs). Transcriptome analysis identified enrichment of HSC but not progenitor gene signatures in MLL-AF9-expressing cells. Although not observed in adult cells, neonatal cells expressing MLL-AF9 were enriched for gene signatures associated with poor prognosis, resistance to chemotherapeutic agents and MYC signaling. These results indicate that neonatal cells are inherently more prone to MLL-AF9-mediated immortalization than adult cells and suggest that intrinsic properties of the cell of origin, in addition to extrinsic cues, dictate lineage of the immortalized cell.

Topics: Animals; Antigens, CD19; Cell Lineage; Cell Transformation, Neoplastic; Female; Hematopoietic Stem Cells; Humans; Infant, Newborn; Leukemia, Myeloid, Acute; Lewis X Antigen; Lipopolysaccharide Receptors; Mice; Mice, SCID; Myeloid-Lymphoid Leukemia Protein; Oncogene Proteins, Fusion; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Resting human NK cells require a two-stage activation process that we have previously described as "priming" and "triggering." NK-sensitive tumor cells provide both priming and triggering signals. NK-resistant tumors evade lysis, mostly by failure to prime; however, we recently reported a tumor cell line (CTV-1) that primes resting NK cells but fails to trigger lysis. In this article, we report two additional leukemia cell lines that prime NK cells but are resistant to lysis. Tumor-mediated NK priming is via CD2 binding to a ligand within CD15 on the tumor cell. NK-resistant RAJI cells became susceptible to NK lysis following transfection and expression of CD15. Blockade of CD15 on K562 cells or on CD15(+) RAJI cells significantly inhibited lysis, as did blockade of CD2 on resting NK cells. NK priming via CD2 induced CD16 shedding, releasing CD3ζ to the CD2, leading to its phosphorylation and the subsequent phosphorylation of linker for activation of T cells and STAT-5 and synthesis of IFN-γ. Blockade of C-type lectin receptors significantly suppressed the tumor-mediated priming of NK cells, whereas blockade of Ig-superfamily-like receptors had no effect at the NK-priming stage. Tumor priming of resting NK cells was irrespective of HLA expression, and blockade of HLA-killer Ig-like receptor interactions did not influence the incidence or degree of priming. However, CD15-CD2 interactions were critical for NK priming and were required, even in the absence of HLA-mediated NK inhibition. Tumor-mediated priming led to a sustained primed state, and the activated NK cells retained the ability to lyse NK-resistant tumors, even after cryopreservation.

Topics: CD2 Antigens; Cell Differentiation; Cell Line, Tumor; Cell Lineage; Coculture Techniques; Cytotoxicity, Immunologic; Disease Resistance; Fucosyltransferases; Humans; Killer Cells, Natural; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Lewis X Antigen; Ligands; Lymphocyte Activation; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Binding; Receptors, KIR; Resting Phase, Cell Cycle; Signal Transduction

The expression of the myeloid markers CD13, CD33, and CD15 in two hundred and eighty-three cases of de novo childhood acute lymphoblastic leukemia (ALL) is examined. The expression of at least one marker is a frequent event which is noted in 64% and 74% of B- and T-lineage ALL cases, respectively. Certain patterns of myeloid antigen expression can be recognized including: no expression of CD13, CD33, and CD15 in mature B-ALL, significantly higher levels of CD13 and CD33 and significantly lower levels of CD15 in TEL-AML1-positive B cell precursor ALL, no expression of CD13 and CD33 in E2A-PBX1-positive B cell precursor ALL cases and common T-ALL (double positive for CD4 and CD8), and no expression of CD13 in MLL-AF4-positive B cell precursor ALL cases. Although the numbers in some ALL subtypes are small, these patterns are consistent with nonrandom expression of myeloid markers in de novo childhood ALL.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Burkitt Lymphoma; CD13 Antigens; Cell Differentiation; Child; Core Binding Factor Alpha 2 Subunit; Homeodomain Proteins; Humans; Lewis X Antigen; Myeloid Cells; Oncogene Proteins, Fusion; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sialic Acid Binding Ig-like Lectin 3

Aberrant expression of myeloid antigens (MyAgs) on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c -- Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases).. In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c) is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used.. We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p < 0.0001), CD33 (p = 0.002) and/or CD65 (p = 0.029). Our data show that different myeloid antigens often differ in biological importance, which may be obscured by combining them into "MyAg positive ALL". We show that unlike other MyAgs, CD66c expression is not shifted from the onset of ALL to relapse (n = 39, time to relapse 0.3-5.3 years). Although opposite has previously been suggested, we show that CEACAM6 transcription is invariably followed by surface expression (by quantitative RT-PCR on sorted cells) and that malignant cells containing CD66c in cytoplasm without surface expression are not found by flow cytometry nor by Western blot in vivo. We report no prognostic significance of CD66c, globally or separately in genotype subsets of B-precursor ALL, nor an association with known risk factors (n = 254).. In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.

Topics: Adolescent; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Blotting, Western; CD13 Antigens; Cell Adhesion Molecules; Cell Membrane; Child; Child, Preschool; Cohort Studies; Cytoplasm; Czech Republic; Disease-Free Survival; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genotype; Glycosylation; GPI-Linked Proteins; Humans; Immunophenotyping; Infant; Lewis X Antigen; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; RNA; Sialic Acid Binding Ig-like Lectin 3; Time Factors; Transcription, Genetic

Programmed cell death, or apoptosis, is a physiological means of eliminating unwanted cells and maintaining immune homeostasis. One of the primary mechanisms is the Fas (CD95)/Fas ligand system. Its inactivation in normal cells and malignant cells may be involved in malignant trans-formation and refractory clinical course, respectively. We established a Fas resistant clone and evaluated the molecular basis for its mechanism of resistance. The Fas-sensitive leukemia cell line, MML-1, was established from a child with B-precursor acute lymphoblastic leukemia. A Fas resistant clone, MML-1R, was obtained by co-culture selection with anti-Fas antibody CH-11. Flow cytometry analysis showed both cell lines had equivalent expression of cell surface CD13, 15, 19, 22 and Fas receptor. Western blot analysis revealed equal expression of FADD (Fas-associated death domain protein), caspase-3 and -8. MML-1 was quite sensitive to both CH-11 and etoposide-induced apoptotis. By contrast, MML-1R had similar sensitivity to etoposide but no response to CH-11. Fas receptor mutation analysis showed a heterozygous death domain A --> G point mutation at 1009 bp, causing a switch from glutamine to glycine at amino acid 256. Immunoprecipitation assay showed decreased binding of Fas to FADD. We also found that etoposide bypassed Fas-FADD interaction in MML-1R by activating caspase-8 and caspase-3. These results indicate that Fas resistance can result from mutations of the gene encoding the Fas receptor which result in decreased FADD binding, thereby blocking formation of the death inducing signaling complex. Screening for similar Fas mutations in therapy resistant malignancies would lead to a better understanding of tumorigenesis and recurrence.

Topics: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Antibodies, Monoclonal; Antigens, CD19; Antineoplastic Agents, Phytogenic; Apoptosis; Base Sequence; Blotting, Western; Caspase 3; Caspase 8; Caspases; Cell Line, Tumor; Child; DNA Mutational Analysis; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Enzyme Activation; Etoposide; fas Receptor; Fas-Associated Death Domain Protein; Flow Cytometry; Humans; Lewis X Antigen; Mutation; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Binding

The abnormality in the translocation of chromosomes 4 and 11 (t[4;11]) has been characteristically associated with calla-negative CD15(+) acute lymphoblastic leukemia (ALL) of early pre-B-cell origin. Transformation of a lymphoblastoid to a monoblastoid morphologic structure has rarely been described at relapse in these cases; however, these cases have lacked flow cytometric immunophenotyping (FCI) and genotypic studies (GS) to define the immunophenotype of and the presence of a B-cell gene rearrangement in the monoblastoid component. We report a case of CD15(+), CD10(-) ALL of early pre-B-cell origin defined by morphologic testing and FCI with the t(4;11) abnormality. At relapse, the morphologic testing, enzyme cytochemistry, and FCI data were characteristic of monoblastic leukemia. The t(4;11) abnormality persisted with associated additional chromosomal abnormalities, and the monoblasts contained a B-cell gene rearrangement by GS. These findings support the concept that both processes arose from a multipotential progenitor cell.

Topics: Antigens, CD; B-Lymphocytes; Blast Crisis; Bone Marrow Transplantation; Chromosome Mapping; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 4; Female; Flow Cytometry; Gene Rearrangement, B-Lymphocyte; Humans; Immunoglobulin Heavy Chains; Immunophenotyping; Leukemia, Monocytic, Acute; Lewis X Antigen; Middle Aged; Neoplasms, Second Primary; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Translocation, Genetic

Discrepancies in the literature on acute leukemia blast cell immunophenotypes are sometimes related to differences between the epitopes recognized by various monoclonal antibodies (MoAb) in the same cluster of differentiation. CD15 is one example of such a variation. CD15 expression has been reported in 1.6% to 39% of acute lymphoblastic leukemias (ALL). We studied the expression of CD15 using 10 different commercially available anti-CD15 MoAbs and we observed three different expression patterns using anti-CD15 MoAbs by flow cytometry in 158 cases of ALL: Smy15c was found in 70% of B lineage ALLs, Smy15a and FMC-13 in 30 to 40% of cases and all others in less than 9% of B-ALL cases (p < 0.0001). In T lineage ALLs, Smy15c, Smy15a and FMC-10 identified CD15 in 30% of the cases and all others in less than 8% of the cases. Logistic regression revealed that Smy15a, CD34 and CD14 correlated significantly with Smy15c expression. We conclude that CD15 MoAbs have to be chosen carefully when ALL immunophenotype and subsequent studies of prognostic significance are performed particularly in assessing multiphenotypic ALLs.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Child; Child, Preschool; Female; Humans; Infant; Lewis X Antigen; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The t(4;11)(q21;q23) characterizes a distinct clinical entity of childhood and adult acute lymphoblastic leukemia (ALL) with a pre-pre-B-phenotype, monocytoid features, coexpression of CD15 and/or CDw65 and a dismal prognosis. The molecular correlate of the t(4;11) has been identified as a fusion transcript of HRX, a gene on 11q23 with homology to drosophila trithorax gene, and FEL, a serine-proline-rich gene on 4q21 of unknown function. The aim of the current study was to establish a reverse transcription-polymerase chain reaction (RT-PCR) approach for the rapid and sensitive detection of the HRX-FEL fusion transcript associated with the t(4;11). For this purpose, two groups of patients were studied: group A comprised cases with cytogenetically proven t(4;11) including three infant and four adult pre-pre-B-ALL, as well as the two cell lines RS4;11 and MV4;11. Group B consisted of ten adult pre-pre-B-ALL with the identical phenotype, but without cytogenetic confirmation of t(4;11). Using primers complementary to HRX and FEL cDNA sequences 300 to 500 bp 5' and 3' of published breakpoints, respectively, specific amplification products were obtained in all nine cases of group A and in nine of the ten cases of group B. Three different types of fusion transcripts were identified by sequence analysis with HRX breakpoints at nucleotides 4086 and 4218 and FEL breakpoints at nucleotides 1413, 1416, and 1458. These data indicate that RT-PCR allows the detection of HRX-FEL fusion transcripts in the vast majority of cytogenetically proven and immunophenotypically suspected t(4;11) ALL. Hence, this technique may allow identification of a further subset of high risk ALL and may also be useful for the monitoring of minimal residual disease in t(4;11) ALL.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Base Sequence; Child; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 4; Humans; Lewis X Antigen; Molecular Sequence Data; Neoplasm Proteins; Polymerase Chain Reaction; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Translocation, Genetic

Several classifications of acute lymphoblastic leukemias (ALL) have been proposed as increasing numbers of technologies and reagents allowed to better characterize leukemic tumor cells. The French Groupe d'Etude Immunologique des Leucémies (GEIL) proposes an immunologic classification of ALL derived from this group's initial attempts and on proposals published by others. Its first step is based on a scoring system where individual markers are assigned major, intermediate and minor weights on a scale of respectively 1.5, 1 and 0.5 points. Assignment to a given lineage requires a score of at least 2 in this lineage. Thus are identified the four levels "null", "pure", "variant" and "multiphenotypic", depending on score combinations in the three B, T and myeloid lineages. In a second step, within each of these classes, cell differentiation criteria are applied to further identify 4 subclasses within PreB-ALL (PreB1 to PreB4) and 4 within T-ALL (T1 to T4). ALL with only myeloid markers are referred to as M0. This classification was applied to a series of 1014 scorable ALL. Pure ALL represented respectively 72% in children under 16, and 64% in adults, PreB ALL being significantly more frequent in the former (p < 0.01). B-ALL and T-ALL were significantly (p < 0.05) more frequent in adults (respectively 11% and 27%) than in children (7% and 20%). Null and M0 ALLs appeared significantly (p < 0.01) more frequent in adults (3.4 and 3.2%) than in children (1 and 0.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, Myelomonocytic; Cell Adhesion Molecules; Child; Child, Preschool; Humans; Immunophenotyping; Infant; Lectins; Lewis X Antigen; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sialic Acid Binding Ig-like Lectin 2; Time Factors

Specific morphological and histochemical changes serve to define stages of differentiation during terminal myeloid maturation. The development of the hybridoma technology has allowed generation of monoclonal antibodies selectively reactive with antigenic determinants expressed in the hematopoietic system by myeloid cells at specific stages of differentiation. Here, the characterization by one of these antibodies i.e. GO35 (CD17) which shows myeloid specificity, was reported on blastic cells from 30% of acute lymphoid leukemia cases investigated (8/25). This monoclonal antibody may prove useful in the subclassification of atypical lymphoproliferative disorders including "hybrid leukemias" and serve as a possible prognostic factor for a therapy.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Child; Child, Preschool; Humans; Lewis X Antigen; Middle Aged; Phenotype; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The prognostic significance of expression of myeloid-associated antigens in childhood acute lymphoblastic leukemia (myA+ALL) was evaluated. From 1984 to 1990, 251 children with immunologically verified ALL were treated in two prospective consecutive Austrian studies. Complete immunophenotyping was performed in 206 cases (82%). Out of these 175 cases were classified as B-cell precursor ALL, 31 cases as T-ALL. Expression of myeloid-associated antigens was demonstrated in 23 cases (13.1%) of childhood B-cell precursor ALL, particularly in immature (CD10 negative) forms (P < .0001), and in 1 case (3.2%) of T-ALL. CDw65 was expressed most frequently (12 cases), followed by CD13 and CD15 (5 cases each), CD33 (4 cases), and blood-group H (3 cases). Compared to myA- ALL prognosis of children with myA+ B-cell precursor ALL was poor, despite intensive multiagent chemotherapy according to BFM protocols. Remission rates were not impaired, but pEFS was 74.6% for myA- ALL, and only 37.8% for myA+ ALL (P = .0001). As demonstrated by multivariate analysis the expression of myeloid-associated antigens was the most important prognostic variable for EFS in B-cell precursor ALL, whether or not CD10 was expressed.

Topics: Adolescent; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Child; Cranial Irradiation; Hemoglobins; Humans; Immunophenotyping; Leukemia-Lymphoma, Adult T-Cell; Leukocytes; Lewis X Antigen; Multivariate Analysis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Prognosis; Prospective Studies; Treatment Outcome

Among 72 Chinese patients with acute lymphoblastic leukemia (ALL), 50 had clonal chromosomal abnormalities. Structural abnormalities were detected in 42 patients: these included t(9;22) in 9, t(1;19) in 6, t(4;11) in 5, del(11)(q23) in 4, and del(6q) in 4. Adults had a higher incidence of t(9;22) and t(1;19) but a lower incidence of t(4;11) and hyperdiploid greater than 50 karyotype than children. A significant difference was also noted in white blood cell (WBC) count among various karyotypic groups. Patients with chromosomal abnormalities t(9;22), t(1;19), t(4;11) and del(11) (q23) had a shorter complete remission duration as compared with patients free of these abnormalities. Immunophenotyping was performed on 69 patients. All patients with t(9;22), t(1;19), and t(4;11) had B-lineage ALL restricted to certain stages of maturation: groups III and IV, groups IV and V, and group II, respectively (according to the classification of Foon and Tood). Among patients with t(9;22), t(4;11), and del(11)(q23), which have been considered to be associated with acute mixed-lineage leukemia, one each, respectively, showed myeloid antigen expression on the leukemic blasts (My+ ALL). No cross-lineage rearrangements of immunoglobulin (Ig) or T-cell receptor (TCR) genes were detected in these karyotypic subgroups of patients who underwent gene analysis.

Topics: Adolescent; Adult; Aged; Antigens, Neoplasm; Blotting, Southern; Bone Marrow Cells; Chi-Square Distribution; Child; Child, Preschool; Chromosome Aberrations; Chromosome Deletion; Chromosomes, Human; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 4; Chromosomes, Human, Pair 9; Female; Gene Rearrangement; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, T-Lymphocyte; Humans; Immunoglobulin Heavy Chains; Infant; Lewis X Antigen; Male; Middle Aged; Polyploidy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Translocation, Genetic; Trisaccharides

Pre-B acute lymphoblastic leukemia (ALL) was diagnosed in 37 children morphologically, histochemically, and by immunophenotyping by flow cytometry. In all patients the leukemic blasts expressed HLA-DR and CD19 (Leu-12). In 10 patients 20% or more of the blast cells expressed a myeloid antigen: CD15 (Leu-M1) in seven, CD33 (My9) in two and CD13 (My7) in one patient. All 37 children achieved complete remission, but eight relapsed. Relapse occurred in six of seven patients with CD15-positive blasts, but in only two of 27 patients with CD15-negative blasts (p = 0.0003). Thus, the occurrence of CD15 on the blasts of children with pre-B ALL shows a remarkable association with a high risk of relapse, and these patients should therefore be considered to belong to the high-risk group regardless of other prognostic factors.

Topics: Adolescent; Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Child; Child, Preschool; Female; Humans; Immunophenotyping; Infant; Infant, Newborn; Lewis X Antigen; Male; Neprilysin; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis

The monoclonal antibody Leu-M1 was originally described as a marker of myeloid/monocytic cells and their precursors. Its usefulness as a myeloid marker in bone marrow specimens was further supported by a limited number of studies using flow cytometry and cell suspensions. Recent reports on its utility in paraffin sections for the diagnosis of acute leukemia have not shown it to be an effective marker of myeloid differentiation. To further evaluate the diagnostic usefulness of Leu-M1 in acute leukemia, we investigated the immunoreactivity of Leu-M1 antigen in a series of 100 plastic-embedded bone marrow biopsies from patients with acute leukemia and compared these results to those obtained in a series of 30 paraffin-embedded specimens. We also investigated the usefulness of neuraminidase pretreatment of sections to enhance the sensitivity of Leu-M1. In plastic sections, we were able to demonstrate positive Leu-M1 staining in 48 of 50 (96%) cases of acute nonlymphoid leukemia (ANL) (FAB classification M1-M5) and 0 of 50 cases of acute lymphocytic leukemia (ALL). Comparatively, Leu-M1 stained positively in 10 of 20 (50%) cases of ANL and 0 of 10 ALL embedded in paraffin. In both plastic and paraffin sections, pretreatment with neuraminidase enhanced the sensitivity of Leu-M1 reactivity, but markedly decreased its specificity. Our study suggests Leu-M1 is both a reliable marker of myelomonocytic differentiation and a useful diagnostic tool in the differentiation of ANL from ALL in plastic sections, and confirms its limited usefulness in paraffin-embedded material.

Topics: Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Diagnosis, Differential; Humans; Leukemia, Myeloid, Acute; Lewis X Antigen; Microtomy; Neuraminidase; Paraffin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Staining and Labeling