Gene/Protein Disease Symptom Drug Enzyme Compound
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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 report describes the analysis of culture cells and blast cells separated from the heparinized bone marrow and whole blood of patients with acute leukemias by means of a density-gradient technique (Ficoll-sodium metrizoate d = 1.077 g/cm3). Cell-surface antigens were analyzed by a fluorescence-activated cell sorter using a panel of monoclonal antibodies (MAbs). The blast cells and culture cells were fixed by 3% paraformaldehyde in phosphate-buffered saline. A low level of expression of MPO precursor protein was found in THP-1. K-562 and HEL, MEG-01, erythro-megakaryocytic leukemia cell lines, Jurkat, MOLT-3, MOLT-4, RPM18402, ATL-5, T-cell leukemia cell lines, Raji, Daudi. BALL-1, B-cell leukemia cell lines, and AGNK1 showed negative reaction. The de novo MPO-negative acute leukemias, middle level of expression of MPO precursor protein, was found in the blasts of MPO-negative AML (AML, M0), which coexpressed CD13, CD33, CD34, and CD38. A high level of expression of MPO protein was found in all cases of AML, M1, and M2. The MPO expression was not found in all cases of acute lymphoblastic leukemia. The highest level of MPO expression was found in cases of AML, M3, and AML, M3v, suggesting the diagnostic value for this type of leukemia. The detection of MPO precursor protein by flow cytometric analysis with monoclonal antibodies is essential for the determination of lineage and precise diagnosis of acute unclassifiable leukemia, and should contribute substantially to the development of an effective form of therapy and cure.
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PMID:Sensitive detection technique of myeloperoxidase precursor protein by flow cytometry with monoclonal antibodies. 966 78

A new cell line with megakaryoblastic features, designated UoC-M1, was established from the malignant cells of a 68-year-old patient with acute myeloid leukemia. The patient's leukemic cells reacted with alpha-naphthyl acetate esterase and acid phosphatase and expressed CD7, CD24, CD34, CD38, CD45, HLA-DR and CD61. Cytogenetic analysis of the patient's malignant cells (and of the UoC-M1 cells) showed a human, male hypodiploid karyotype with many chromosome rearrangements and marker chromosomes. Spectral karyotyping (SKY) analysis complemented the G-banded karyotyping and clarified several chromosomal translocations and identified the marker chromosomes. Fluorescence in situ hybridization (FISH) and SKY analysis demonstrated that one marker chromosome contained three segments of chromosome 9 interspersed with three segments of chromosome 11, as well as a portion of chromosome 19. FISH analysis with a probe for MLL revealed that the UoC-M1 cells contained four copies of the MLL gene. Southern blot analysis determined that the MLL gene had a germline profile while Northern and Western analyses showed that the MLL mRNAs and protein were of the appropriate sizes. This is the first report of amplification of the MLL gene which may be an additional mechanism of leukemogenesis or disease progression.
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PMID:Establishment and characterization of a megakaryoblast cell line with amplification of MLL. 966 99

We investigated the expression-percentage as well as MESF values ("molecules of equivalent soluble fluorochrom" that represent approximately the density of marker expression) of HLA-DR, CD71 and CD38 markers in some human leukemias (ALL, AML, CLL, CML) and lymphomas. They are non-lineage restricted and are supposed to be activation markers except for cases where they represent pathological phenotype like HLA-DR in pre B-ALL, CD38 in some M0 AML or in plasmocytoma or CD38 and CD71 in less mature T-ALL. We used flow cytometry, immunofluorescent staining, DNA staining by propidium iodide and quantification by calibration particles. We demonstrated increased MESF values of HLA-DR compared with controls in all investigated disorders, what could have a prognostic value. We demonstrated significantly higher MESF values of HLA-DR in cALL (37,300-46,000) in comparison with AML (9400-12,400), what could represent another important parameter when distinguishing between these two groups of leukemia. In cells of CML patients with lower CD38% and CD71% increased MESF values (5100 for CD38 and 7900 for CD71), were found while in some T-ALL, AML and cALL patients with high percentages of CD71 and CD38 there were lower MESF values what could indicate a possible connection of higher stage of cell maturation with increased density of CD38 and CD71 markers. We investigated possible relationship between percentage of expression of HLA-DR, CD38 and CD71 and proliferation rate by DNA analysis of the cell cycle. In a group of non-Hodgkin's lymphoma patients, there was no significant increase of proliferation index of malignant cells compared with control. The correlation between percentage of expression of mentioned parameters and proliferation index was not significant. In one patient with Burkitt's lymphoma we demonstrated significant increase of proliferation index of CD71+ subpopulation compared with CD71- one, what indicates that in aggressive form of NHL CD71 can be evaluated not only as activation but also as proliferation marker.
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PMID:The relationship of HLA-DR, CD38 and CD71 markers to activation, proliferation and differentiation of some human leukemia and lymphoma cells. 968 89

CD38 is expressed during early stages of differentiation in normal and leukemic myeloid cells. Recently, CD38 has been shown to participate in intracellular signal transduction pathways following its ligation with CD38-specific mAbs. In this study we report that ligation of CD38 by one such agonistic mAb (IB4) induced proliferation of cultured leukemic cells in vitro. In HL-60, KG-1A, NB4, and OCI-AML-3 myeloid leukemia cell lines, IB4 mAb induced an increase in the proliferating cell fraction as determined by cell number, clonogenic assay, and flow cytometric analysis. The presence of Ab caused a dose-dependent increase in the number of CFU and an increase in cell divisions. HL-60-Dox cells (a HL-60-doxorubicin-resistant cell line), which have no detectable CD38 expression, failed to respond to IB4 mAb. The effect of CD38 ligation on cell growth was also evaluated in freshly isolated leukemic cells from patients with acute myelogenous leukemia (AML). A significant increase in the proliferating cell fraction (S+G2M) was observed in 50% of the patients incubated with IB4 mAb. In five of the six AML patients, anti-CD38 mAb stimulated the proliferation of AML colony-forming cells. These results suggest that ligation of CD38 can induce the proliferation of leukemic cells and may play a role in the propagation of leukemic cell clones in certain cohorts of AML patients.
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PMID:Ligation of cell surface CD38 protein with agonistic monoclonal antibody induces a cell growth signal in myeloid leukemia cells. 979

Acute myeloid leukemia (AML) occurs as the result of malignant transformation in a hematopoietic progenitor cell, which proliferates to form an accumulation of AML blasts. Only a minority of these AML cells are capable of proliferation in vitro, suggesting that AML cells may be organized in a hierarchy, with only the most primitive of these cells capable of maintaining the leukemic clone. To further investigate this hypothesis, we have evaluated a strategy for purifying these primitive cells based on surface antigen expression. As an in vitro endpoint, we have determined the phenotype of AML progenitor cells which are capable of producing AML colony-forming cells (CFU) for up to 8 weeks in suspension culture (SC) and compared the phenotype with that of cells which reproduce AML in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. AML cells were fluorescence-activated cell sorted (FACS) for coexpression of CD34 and CD71, CD38, and/or HLA-DR and the subfractions were assayed in vitro and in vivo at various cell doses to estimate purification. While the majority of primary AML CFU lacked expression of CD34, most cells capable of producing CFU after 2 to 8 weeks in SC were CD34(+)/CD71(-). HLA-DR expression was heterogeneous on cells producing CFU after 2 to 4 weeks. However, after 6 to 8 weeks in SC, the majority of CFU were derived from CD34(+)/HLA-DR- cells. Similarly, the majority of cells capable of long-term CFU production from SC were CD34(+)/CD38(-). Most cells that were capable of engrafting NOD/SCID mice were also CD34(+)/CD71(-) and CD34(+)/HLA-DR-. Engraftment was not achieved with CD34(+)/CD71(+) or HLA-DR+ subfractions, however, in two patients, both the CD34(+) and CD34(-) subfractions were capable of engrafting the NOD/SCID mice. A three-color sorting strategy combining these antigens allowed approximately a 2-log purification of these NOD/SCID leukemia initiating cells, with engraftment achieved using as few as 400 cells in one experiment. Phenotyping studies suggest even higher purification could be achieved by combining lack of CD38 expression with the CD34(+)/CD71(-) or CD34(+)/HLA DR- phenotype. These results suggest that most AML cells capable of long-term proliferation in vitro and in vivo share the CD34(+)/CD71(-)/HLA-DR- phenotype with normal stem cells. Our data suggests that in this group of patients the leukemic transformation has occurred in a primitive progenitor, as defined by phenotype, with some degree of subsequent differentiation as defined by functional assays.
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PMID:Most acute myeloid leukemia progenitor cells with long-term proliferative ability in vitro and in vivo have the phenotype CD34(+)/CD71(-)/HLA-DR-. 983 39

Acute myeloid leukemia arises from the clonal expansion of a malignant transformed progenitor cell. Despite intensive chemotherapy, final disease eradication is achieved by a small proportion of cases only and 50-70% of adults with AML will ultimately relapse and die from their disease. Hence residual disease below the level of morphological detectability must be assumed in clinical and morphological complete remission. CD34+/CD38- and CD34+/CD38+ subpopulations of seven patients in morphological complete remission were isolated by FACS (purity >98%) and were analyzed by conventional cytogenetics or FISH for chromosomal aberrations. In five of seven patients, clonal chromosomal abnormalities were detected in the CD34+/CD38+ subpopulation and in one patient with AML M2 (add (2)(q37)) in the most immature CD34+/CD38- stem cell compartment. One patient with AML M4Eo (inv(16),+8), showed a normal karyotype by conventional cytogenetic analysis, whereas four of 15 metaphases of the sorted CD34+/CD38+ subpopulation revealed the inversion 16. These observations underline that leukemic cells can survive intensive chemotherapy in the niche of the stem cell compartment. In some patients the sensitivity for the detection of persistent leukemic cells seems to be higher in FACS-sorted subpopulations than conventional cytogenetic analysis of the unseparated bone marrow. Immunophenotyping revealed minimal residual disease in four of the patients. Functional analysis has to be performed to investigate the leukemogenic potential of these residual cells.
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PMID:Clonal chromosomal abnormalities in the stem cell compartment of patients with acute myeloid leukemia in morphological complete remission. 1008 29

Minimally differentiated acute myeloid leukemia (AML-M0) is a rare FAB subtype (2-3% of AMLs) of poor prognosis. The aim of our study was to characterize AML-M0 expression and regulation of adhesion/costimulatory molecule involved in immune recognition, to test blast in vitro immunogenicity, and to determine the percentage of leukemia progenitor cells. Here, we demonstrate that alloimmune recognition of AML-M0 in primary mixed lymphocyte reaction, as evaluated by IL-2 secretion of responding T cells, is reduced in comparison with more differentiated subtypes (128 +/- 95 pg/ml vs304 +/- 159 pg/ml, P < 0.05). These data are in line with low blast cell expression of major histocompatibility complex (MHC) class II DR molecules, and of the CD28 ligand B7-2, which plays an important role in AML immune recognition. Adhesion/costimulatory molecules were up-regulated by leukemic cell stimulation via CD40, and, although less efficiently, by gamma-IFN; both stimuli improved blast cell immunogenicity. We also demonstrate that AML-M0 have a very high percentage (40% +/- 30) of CD34+/CD38- leukemic clonogenic precursors in comparison with more differentiated AMLs (2.5% +/- 2) or non-leukemic CD34+hematopoietic precursors (1.8% +/- 0.8). Since the presence of a leukemic cell population at an early differentiation stage has been identified as a poor prognostic factor, we conclude that the high frequency of CD34+/CD38- blasts in AML-M0 may converge with already identified poor prognosis factors such as chemotherapy resistance and cytogenetic abnormalities. The clinical implications of AML-M0 impaired in vitroimmunogenicity and a high percentage of CD34+/CD38- blasts will require comparative analysis of additional patients. The increased immunogenicity of blast cells after CD40 triggering provide interesting clues for AML-M0 immunotherapy, that have to be confirmed with an in vivo leukemia model in mice.
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PMID:The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): reduced immunogenicity and high frequency of CD34+/CD38- leukemic progenitors. 1051 51

Acute promyelocytic leukemia (APL) represents a subtype of acute myeloid leukemia with characteristic morphologic, molecular, and immunophenotypic features. Previous immunophenotypic analyses have shown that leukemic cells in APL typically express the myeloid markers CD33 and CD13 but lack expression of the early hematopoietic progenitor cell antigens CD34 and HLA-DR. We analyzed selected immunophenotypic features of APL by flow cytometry and showed that 7 (41%) of 17 cases contained significant subsets of CD34+ leukemic cells: CD34+ myeloid cells predominated in 2 APL cases. By using a fluorescence-activated cell sorter-fluorescence in situ hybridization approach, we confirmed that the CD34+ cells harbored the t(15;17) translocation characteristic of APL. By using the same experimental approach, CD34+ populations were stratified into primitive CD34+ CD38- and committed CD34+ CD38+ progenitor cell subpopulations; cells in both subsets contained the t(15;17) translocation. The knowledge that APL may be partly or largely CD34+ is important for proper diagnosis. Furthermore, identification of the t(15;17) translocation in CD34+ CD38- blasts indicates that, in at least some cases, the leukemogenic mutation in APL occurs within primitive hematopoietic progenitor cells.
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PMID:Evidence for early hematopoietic progenitor cell involvement in acute promyelocytic leukemia. 1058 5

CD38 is a transmembrane molecule whose expression varies during hematopoietic cell differentiation. We used stroma-supported cultures of human myeloid cells to assess the effects of CD38 ligation on myeloid differentiation. In 8 experiments with CD34(+ )cells purified from normal bone marrow or cord blood, flow cytometry used with antibodies to CD34 and myeloperoxidase (MPO) identified 4 cell populations after 7 days of culture. Addition of anti-CD38 (T16) to the cultures induced a profound reduction of the most mature (CD34(-)MPO(++)) cell population, which includes promyelocytes, myelocytes and metamyelocytes; mean (+/- SD) cell recovery was 12.8% +/- 9.8% of that in parallel cultures with an isotype-matched control antibody. The suppressive effect of CD38 ligation on phenotypically more immature normal cells was inconsistent but generally less pronounced. Recovery of CD34(++)MPO(-) cells was 63.3% +/- 24.4%, recovery of CD34([+/-] )MPO(- )cells was 95.3% +/- 35.1%, and recovery of CD34(-)MPO(+) cells was 42.0% +/- 18.7% of that in control cultures. However, anti-CD38 suppressed recovery of cells obtained from 6 patients with CD38(+) acute myeloid leukemia; after 7-day cultures, cell recovery was 25.2% +/- 21.7% of that in control cultures. Cell recovery was also reduced by F(ab')(2) or Fab fragments of anti-CD38. CD38 ligation dramatically suppressed recovery of murine 32D myeloid cells transfected with human CD38 and cocultured with stroma (3.8% +/- 7.3%; n = 7). CD38 ligation of CD38( + )32D cells also induced cell aggregation, tyrosine kinase activity, and Ca(++) influx. We conclude that CD38 mediates signals that culminate in suppression of myeloid cell growth and survival. (Blood. 2000;95:535-542)
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PMID:CD38 ligation inhibits normal and leukemic myelopoiesis. 1062 59

CD38 is expressed in acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) blasts and its prognostic significance is unknown. We investigated CD38 expression in 304 AML and 138 ALL patients. CD38 was lower in AML-M3 compared to other FAB subtypes (5% vs. 41%; P < 0.001), but was similar among ALL subtypes (56.6%; P = 0.69). Ph + ALL and AML with t(15; 17) patients showed lower CD38 expression than the other cytogenetic groups. Overall survival favored AML and ALL patients with higher CD38 levels. Multivariate analysis revealed CD38 expression to be an independent outcome predictor in AML, but not in ALL.
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PMID:Increased CD38 expression is associated with favorable prognosis in adult acute leukemia. 1065 51


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