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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assesses the value of immunologic and ultrastructural methods in disclosing the lineage commitment of cells from acute leukemias (ALs). Two hundred and fifty-one ALs were characterized morphologically, cytochemically, and immunologically. Myeloperoxidase (MPO) positivity in > 3% of blasts was regarded as evidence of the myeloid origin of leukemic cells, cytoplasmic CD22 (cCD22) expression was taken as an indication for B-lineage acute lymphoblastic leukemia (ALL), and CD3+ (membrane or cytoplasmic) cases were classified as T-ALL. Diagnosis of minimally differentiated acute myeloid leukemia (AML-M0) was made when blast cells had undifferentiated features by light microscopy, reacted with at least one of the antibodies to myeloid-specific antigens (CD13, CD33, MPO), and lacked CD19, cCD22, and c/mCD3. Megakaryoblastic differentiation was demonstrated by the expression of CD41 and/or CD61. Following these criteria, 209 cases were classified as acute myeloid leukemia (AML) and 39 as ALL. Expression of lymphoid antigens was detected in 45% of AML cases and 30% of ALLs showed myeloid antigens. One case was regarded as a true biphenotypic leukemia because of the combined expression of MPO and CD33 for the myeloid lineage, and cCD3, CD2, and CD5 for the T-cell lineage. Two cases lacked signs of myeloid or lymphoid differentiation and were studied by electron microscopy methods. One displayed platelet peroxidase (PPO) activity and was classified as a megakaryoblastic variant, one other reacted with anti-CD33 and was considered AML-M0. We conclude that light microscopy and standard immunologic methods can accurately demonstrate the lineage orientation in greater than 99% of ALs. Integration with ultrastructural analysis can define the cell nature of virtually all cases of AL.
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PMID:Lineage identification of acute leukemias: relevance of immunologic and ultrastructural techniques. 755 58

We have investigated the compartmentalization of aminopeptidase-N-like activity in various blood fractions obtained from patients with acute lymphoid (ALL) or myeloid (AML) leukemia. The primary difference appears not to be the absolute level of overall activity, but rather the relative proportions of the different forms of activity detected. Thus, despite similar levels of total aminopeptidase-N-like activity detected in cells from different leukemic groups, true aminopeptidase-N/CD13 activity was only detected in cells derived from AML patients. Even in these patients, however, most of the detected aminopeptidase-N-like activity ( > 80%) could not be attributed to aminopeptidase-N/CD13. In marked contrast, plasma from leukemic patients also contained substantial total aminopeptidase-N-like activity, of which (irrespective of leukemic group) most could be attributed to aminopeptidase-N/CD13. Whilst slightly higher levels of total activity were obtained in plasma from AML patients compared to ALL patients, there was no difference in the relative proportion attributable to aminopeptidase-N/CD13 (approximately 80% of total aminopeptidase-N-like activity). Evaluation of total aminopeptidase-N-like activity present in whole blood gave differential patterns, and whilst only a proportion (20-40% of total aminopeptidase-N-like activity) could be attributed to true aminopeptidase-N/CD13, blood from patients with CD13+ AML showed the greatest activity so attributable. In total, our results outline the complexities of peptidase activities present within blood of leukemic individuals, and may, in part, explain the variability of previous studies attempting to associate prognostic features with phenotypic expression of CD13.
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PMID:Aminopeptidase-N (CD13; gp 150): contrasting patterns of enzymatic activity in blood from patients with myeloid or lymphoid leukemia. 756 77

Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid-associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.
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PMID:Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87. 757 4

Peripheral blood or bone marrow of 24 patients with chronic myeloid leukemia (CML) were characterized for their surface membrane marker profiles using flow cytometry and fluorescence microscopy. Purine metabolism enzyme activities were compared with membrane immunophenotype and cytochemical stains. CML subtypes were correlated with the expression of surface membrane antigens detected by the monoclonal antibodies. On the basis of immunophenotyping we found the following characteristic marker profiles: In stable phase of CML (CML-SP)-CD15, CD11b, CDw65, CD13, in accelerated phase of CML (CML-AP)-CD15, CDw65, CD11b, CD13 and CD33, in myeloid blastic phase of CML(CML-BP-M)-CD13, CD33, HLA-DR, CD11b, CD15, CDw65, in myeloid and lymphoid (mixed) blastic phase of CML (CML-BP-M+L)-CD13, CD33, CD34, HLA-DR, CD11b, CD10 and in chronic myelomonocytic leukemia (CMML)-CD14, CDw65, CD11b, CD33 and HLA-DR. Analysis of purine metabolism enzyme activities showed that there was a correlation between the values of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and various types of CML. ADA levels in CML-SP, CML-AP and CMML were comparable with those in normal cells. In CML-BP-M, which represents proliferation of less mature myeloid cells (similar to less mature AML subtypes), ADA activity increased and PNP activity decreased. ADA activity was significantly different between control group and CML-BP-M (p < 0.01), between CML-SP and CML-BP-M (p < 0.05). The values of PNP activity were the highest in stable phase of CML (125 pkat. 10(-6) cells) and the lowest (23 pkat.10(-6) cells) in CML-BP-M+L. PNP activity in the other groups corresponded to control values. High ADA/PNP ratio was found in CML-BP-M and CML-BP-M+L (0.7 and 2.0, respectively) in comparison to CML-SP (0.2). It follows from our results that ADA/PNP ratio enables to discriminate between stable and blast phases of CML (p < 0.01). The level of the cytochemical enzymes (CHAE, MPO, SBB, ANAE and 5' NT) varied and reflected the degree of cell differentiation and maturation. CHAE and MPO were characteristic enzymes for CML, ANBE for CMML and 5' NT for CML-BP-lymphoid.
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PMID:Chronic myeloid leukemia: correlation between purine metabolism enzyme activities and membrane immunophenotype. 761 76

In the period from August 1991 to August 1994, the Dutch Slide Review Committee of Adult Leukemias classified 14 leukemias as AML-M0. We reviewed the clinical characteristics and response to therapy of these patients. Eight patients were male. Patients' age ranged from 7 to 77 years (medium age 62 years). There was a striking homogeneity in morphological appearance of the blasts, being small to medium-sized round cells with often an eccentric nucleus with fine chromatin, several distinct nucleoli, and a high nucleo-cytoplasmic ratio. In addition to myeloid-associated markers such as CD13 and CD33, the blasts of all patients were positive for CD34 and HLA-DR, pointing to their immature differentiation stage. TdT was present in the blasts of 71%, CD7 was positive in the blasts of 42% of the patients. No consistent cytogenetic abnormalities were found. With respect to the treatment outcome, four patients achieved a complete remission after remission-induction treatment. The median survival was 4.5 months. Our present study shows AML-M0 to be an immature leukemia, uniform in morphology and immunological phenotype, with no consistent cytogenetic phenotype and with a poor clinical outcome.
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PMID:AML-MO: clinical entity or waste basket for immature blastic leukemias? A description of 14 patients. Dutch Slide Review Committee of Leukemias in Adults. 763 8

Individuals with Down syndrome have an increased incidence of leukemia compared to the general population. In addition, Down syndrome children may acquire a myeloproliferation that resembles acute leukemia that undergoes a spontaneous, durable remission. To clarify the relationship between these two disorders, the morphologic, immunophenotypic and cytogenetic characteristics of 28 patients with Down syndrome and the morphologic manifestations of acute leukemia were examined. Three cytomorphological groups were discerned. The first two groups consisted of five patients with acute lymphoblastic leukemia (group I) and three patients with acute myeloid leukemia (group II). These leukemias resembled those of non-Down individuals. The third and largest group (group III) consisted of 20 cases of acute myeloid leukemia that showed prominent megakaryocytic and/or erythroid differentiation and occurred in children under 6 years of age. The blasts in this group were non-reactive for myeloperoxidase or non-specific esterase and expressed CD7, CD34 and CD36 with variable expression of CD61, CD13 and CD33. Four patients in this group had an acquired trisomy 8. Four group III leukemias underwent a durable, spontaneous remission within 2 months of diagnosis. There were no morphologic differences between those leukemias in this group that progressed and those that remitted; however, all remissions occurred in newborns. It is concluded that Down syndrome children acquire a characteristic acute myeloid leukemia that has prominent megakaryocytic and/or erythroid differentiation and an unusual immunophenotype. This group of leukemias may undergo a durable, spontaneous remission in the newborn period.
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PMID:Acute leukemia and the transient myeloproliferative disorder associated with Down syndrome: morphologic, immunophenotypic and cytogenetic manifestations. 765 8

Acute leukaemia of infancy is associated with abnormalities at chromosome band 11q23, and has a poor prognosis. The gene involved. Mixed Lineage Leukaemia (MLL), has been identified and has the characteristics of a transcription factor. The BCL-2 gene responsible for blocking of programmed cell death is highly expressed in a number of haematological malignancies, both with and without the t(14;18) translocation. Those without the translocation include acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL). In these diseases the BCL-2 protein is implicated in drug resistance to apoptosis-inducing chemotherapeutic agents. High BCL-2 expression is also associated with autonomous growth of leukaemic blasts in culture and predicts a poor prognosis. The SEM cell line, established using blood lymphoblasts from a 5-year-old girl in first relapse with t(4;11) ALL, expresses lymphoid (CD19) and myeloid (CD13) cell surface markers. In cell culture, a subpopulation of cells (< 30%) express the BCL-2 protein. A reproducible model of true biphenotypic leukaemia in the SCID mouse has been established using the SEM-K2 cell line (a subclone of the SEM cell line). Between 5 and 50 million cells injected intravenously (i.v.) produce complete replacement of the murine bone marrow by day 30, associated with blood lymphoblastosis and infiltration of the spleen. No tumour masses were seen. Fluorescence in situ hybridization (FISH) analysis of the cell line and blood from the SCID-human (SCID-hu) chimaera has confirmed the presence of the t(4;11). Reverse transcriptional-polymerase chain reaction (RT-PCR) reveals that the breakpoint lies between exons 7 and 8 of the MLL-1 gene on chromosome 11 (the main breakpoint region). A further translocation, t(7;13), has been identified. Fluorescent antibody cell sorter (FACS) analysis of tumour material recovered from the SCID-hu model confirms expression of CD19 and CD13 identical to that of the cell line. In addition, BCL-2 expression in SCID-hu marrow is now seen in the majority of tumour cells. BCL-2 expression appears to confer a survival advantage to the blast cells in vivo. This reproducible model of biphenotypic leukaemia suggests that BCL-2 expression may play a role in leukaemogenesis. The model is suitable for the investigation of gene-targeted therapy, including antisense oligonucleotides, directed towards the MLL and BCL-2 genes.
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PMID:BCL-2 expression by leukaemic blasts in a SCID mouse model of biphenotypic leukaemia associated with the t(4;11)(q21;q23) translocation. 766 64

One of 8 to 12 pre-B ALL cells co-express CD13 and CD33 antigens, but such blasts do not express myeloperoxidase (MPO) even on electronmicroscopy or mRNA. MPO+ pre-B ALL is extremely rare (1/50-1/100), however a cell-line (Tahr87) was established in culture. In contrast, T-lineage blasts express CD13/33 antigens regularly in the pro-thymic stage (CD7+ 5+ 2+ 3- 4- 8- or more immature), and a limited expression of MPO is rather commonly detected particularly in recurrences. The co-expression of CD3 epsilon/MPO or CD3 epsilon/delta/MPO mRNA has been demonstrated. Thus, the regulation of MPO expression is of utmost importance in interpreting the phenotypes of leukemia/lymphoma. While testing the effects of several cytokines on MPO expression, IFN-gamma was found to suppress the gene expression of MPO in HL60 cells. This suppression was not accompanied by differentiation, termination of proliferation or reduction of cytochemical MPO+ cells, and was reversible. Among 22 cases of M1 AML blasts, 8 cases were HLA-DR(-). DR antigen was induced by the presence of a mixture of IFN-gamma, TNF-alpha and TPA in 4 cases, but not in the other 4 cases. The blasts of the latter 4 cases were always CD34(-), CD7(-) and CD45RA-/RO+, and constituted a distinct M1 subset which has not previously been reported.
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PMID:[Cytokine in phenotypic analysis of leukemia/lymphoma: suppression of gene expression of myeloperoxidase by IFN-gamma and subset of AML M1 defined by CD45RO+/RA-, CD7(-), CD34(-) and non-inducible HLA-DR antigen]. 768 32

A study of immunological markers was performed in 16 patients with newly diagnosed refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) and in 12 other patients with acute myeloid leukaemia evolving from RAEB or RAEB-T. Immunocytochemical investigation of bone marrow blasts was done using a modified indirect immunoperoxidase technique. This method permitted accurate morphological identification of blasts and other cells in bone marrow. The monoclonal antibodies used in RAEB and RAEB-T samples were anti-CD34, -c-kit, -HLA-DR and -CD13. The range of CD34 expression of blasts in RAEB samples was 1-14% (mean 6.2%) and in RAEB-T samples 29-48% (mean 35.5%). CD34 positivity was detected in 3-94% (mean 47.4%) of the bone marrow blasts in acute myeloid leukaemia evolving from RAEB and RAEB-T. Expression of c-kit was demonstrated only in a low percentage of blast cells in RAEB, RAEB-T and acute myeloid leukaemia following myelodysplasia. A high percentage (> 30%) of blasts in most patients with RAEB, RAEB-T and acute myeloid leukaemia was HLA-DR and CD13 positive. We observed the transformation from RAEB to acute myeloid leukaemia in three patients. The proportion of CD34 positive blasts increased to 25% and 32% in two patients. The third patient showed an unchanged percentage of CD34 positivity of blasts. These findings indicate that the CD34 positivity of blasts increases with the progression of myelodysplasia to RAEB-T and acute myeloid leukaemia demonstrating the instability of the clonal defect in myelodysplasia.
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PMID:Immunotyping of blasts in refractory anaemia with excess of blasts. 769 Nov 47

We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML-M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML-M6. Thirty-three patients (63%) were male, median age 59 (range 16-81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of < 2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin-A, and HLA-DR markers. Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (< 3 karyotypic abnormalities), while 9 (33%) were complex (> or = 3 abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML-M6 were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts > 25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophilic erythroblasts < or = 25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid-Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML-M6 is typified by multilineage involvement of hematopoietic cells. The morphology of erythroblasts in patients with AML-M6 may correlate with cytogenetic abnormalities and rate of CR.
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PMID:Morphologic characteristics of erythroleukemia (acute myeloid leukemia; FAB-M6): a CALGB study. 774 Nov 35


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