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)

Major histocompatibility complex-unrestricted lymphokine-activated killer (LAK) cells have been proposed as therapy for a variety of hematologic malignancies. Because these cells recognize and kill their targets independently of their antigen specific CD3 receptor, it is unclear how they might discriminate between normal and malignant cells. We now propose one such mechanism for the selective killing of myeloid leukemia blasts. While both CD2+ and CD2- activated killer cells may inhibit the clonogenic growth of myeloid leukemia cells, only the CD2+ subset effectively inhibits the growth of normal myeloid (granulocyte-macrophage and granulocyte) progenitors. This difference appears to reflect differential requirements for cell adhesion molecule recognition between normal and malignant progenitor cells. Inhibition of the growth of normal granulocyte-macrophage colonies by CD2+ LAK cells is blocked by antibodies to the CD2-lymphocyte function-associated antigen 3 (LFA-3) (CD58) cell adhesion system. In contrast, these antibodies have no effect on CD2+ LAK-mediated inhibition of malignant cell clonogenic growth. Instead, antibodies to the LFA-1 (CD11a/CD18)-intercellular adhesion molecule 1 (ICAM-1) (CD54) adhesion system reduce inhibition. These differences correspond to differential expression of the CD54 cell adhesion molecule by normal and malignant myeloid progenitor cells because less than 15% of normal CD34 positive cells are CD54+ while greater than 85% of CD34+ acute myeloid leukemia blasts express the CD54 antigen. LFA-3, the ligand for CD2, is strongly expressed by erythrocytes, and these cells competitively inhibit killing of normal but not malignant clonogenic cells in an analogous way to the effects of monoclonal antibody to the CD2-LFA-3 adhesion system. The operation of this effect in vivo may be a basis for selective cytotoxicity by CD2+ LAK against clonogenic myeloid blast cells, and could be exploited further with infusion of appropriate monoclonal antibodies.
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PMID:Possible mechanism of selective killing of myeloid leukemic blast cells by lymphokine-activated killer cells. 170 96

We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34-positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL-6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3-dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.
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PMID:Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia. 171 40

The c-kit proto-oncogene product is a member of the family of growth factor receptors with intrinsic tyrosine kinase activity. In the mouse c-kit maps to the W locus, which is known to be of central importance in hematopoiesis. Monoclonal antibody (MoAb) YB5.B8, which was raised against peripheral blood blast cells from a patient with acute myeloid leukemia (AML), was recently shown to bind to the extracellular domain of the c-kit product. This antibody does not bind detectably to normal peripheral blood cells and identifies a sub-group of AML patients with poor prognosis. We have used MoAb YB5.B8 to study the expression of c-kit by normal human bone marrow cells by immunofluorescence and flow cytometry, and to isolate multipotential and erythroid colony-forming cells. In a series of 11 normal adult bone marrow specimens, MoAb YB5.B8 bound to 4.0% +/- 1.8% of the cells in the low-density fraction. Dual-labeling experiments were performed with YB5.B8, and CD33, CD34, and CD10 MoAbs. Three populations of cells binding YB5.B8 could be identified based on their pattern of coexpression of the other markers; ie, YB5.B8+/CD34+/CD33-, YB5.B8+/CD34+/CD33+ and YB5.B8+/CD34+/CD33+. These populations had distinctive two-dimensional light scatter characteristics and are likely to correspond to precursor colony-forming cells, colony-forming cells, and maturing mast cells, respectively. No cells binding both YB5.B8 and an MoAb to the early lymphoid marker CD10 were found, implying that most early lymphoid cells do not express c-kit. MoAbs to the c-kit protein should prove valuable in multimarker studies of human hematopoietic stem and progenitor cells. Definition of a reference range of c-kit expression in normal human bone marrow will provide a sound basis for further studies of this marker in diagnosis and prognosis in AML.
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PMID:Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow. 171 44

Among 52 patients diagnosed as acute myeloid leukemia (AML), nine cases were found in which interleukin-5 (IL-5) induced a proliferative response in the leukemic cells, as measured by the stimulation of DNA synthesis or colony formation in vitro. All cases (n = 7) with the cytogenetic abnormality t(8;21)(q22;q22) belonged to this group of IL-5 responders. Of the additional two cases, one had an apparently normal karyotype, but the other expressed a dicentric chromosome 21, an abnormality also involving the breakpoint region 21q22. The leukemic cells of the IL-5 responsive patients could also be stimulated to proliferate by IL-3, GM-CSF and G-CSF, and in some cases by IL-6 or M-CSF. Immunophenotypic analysis revealed the presence of the immature hematopoietic cell antigen CD34, the myelomonocytic maturation antigens CD13 and CD33, in association with the B-cell related surface marker CD19 on the leukemic cells. Immunoglobulin mu and T-cell receptor beta-genes in the leukemic cells were in germline configuration. Upon incubation in colony culture, clonogenic cells were capable of producing progeny showing eosinophilic or neutrophilic maturation following stimulation with IL-5 or G-CSF, respectively. It is concluded that IL-5 responsive AML represents a subgroup of leukemia with distinct immunotypic and cytogenetic features.
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PMID:Acute myeloid leukemias with chromosomal abnormalities involving the 21q22 region identified by their in vitro responsiveness to interleukin-5. 171 59

Two members of the src proto-oncogene family of intracellular tyrosine kinases, c-fgr and hck, are selectively expressed in differentiated myeloid cells. To study the expression of these genes in acute myeloid leukemia (AML) and to determine the specific myeloid lineages and stages of myeloid differentiation at which the expression of these genes is acquired, we used a series of 79 cases of de novo AML as a differentiation model. The levels of c-fgr, hck, and c-fms (encoding the colony-stimulating factor-1 receptor) mRNA transcripts were correlated with the presence of specific cell surface antigens and the morphologic and cytochemical features in these AML blasts. Relatively undifferentiated leukemic myeloblasts with an HLA-DR, CD34, CD33, CD13+/- cell surface immunophenotype (French-American-British [FAB] M1 or M2) were characterized by a lack of c-fms and c-fgr expression, while low levels of c-fms and c-fgr could be detected in undifferentiated myeloblasts (FAB M1 or M2), which also expressed CD14 at low antigen density. The hck transcripts were either undetectable in these cells or were expressed at low levels. In contrast, only hck mRNA transcripts could be identified in blasts with progranulocytic morphology (FAB M3), while c-fms, c-fgr, and hck were all expressed at high levels in blasts with differentiated myelomonocytic or monocytic features (FAB M4 and M5). No c-fms, c-fgr, or hck transcripts were evident in leukemic cells of the erythroid lineage (FAB M6). When undifferentiated leukemic myeloblasts (HLA-DR, CD34, and CD33) were induced to differentiate in vitro to cells with monocytic characteristics, the expression of c-fms, c-fgr, and the CD14 cell surface antigen were induced to high levels, accompanied by the acquisition of hck and CD13 expression. In contrast, when HLA-DR, CD34, and CD33 blasts were induced to differentiate in vitro to cells with granulocytic characteristics, only hck and CD13 expression were induced. Our data suggest that the acquisition of c-fgr and/or hck expression is associated with early commitment and differentiation events in distinct myeloid lineages. Assessment of the expression of these kinases may provide a molecular tool to assign lineage in AML in conjunction with morphology, cytochemistry, and cell surface antigen expression.
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PMID:Expression of the c-fgr and hck protein-tyrosine kinases in acute myeloid leukemic blasts is associated with early commitment and differentiation events in the monocytic and granulocytic lineages. 182 81

Eight cases of acute myelogenous leukemia with (8; 21) translocation were reported. As recently reported, they showed following features: M2 morphology in FAB classification (all 8 patients), abnormal granulocyte maturation, i.e. large granules and pseudo Pelger-Huet forms (5), Auer rods (8), occasional eosinophilia (2), frequent loss of one sex chromosome (5), the low neutrophil alkaline phosphatase activity (5), and tumor formation (one). Both CD13 and CD33 antigens were expressed on smaller number of leukemic cells than the other AML (M2) cells, whereas CD34 and HLA-DR antigens were expressed on higher number of cells. Interestingly CD19 antigen was detected on a small to large population of tumor cells from four out of six patients. Despite the high remission rate, many of them relapsed within one year. More intensive postinduction and maintenance therapy should be considered for those patients.
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PMID:[Clinical and cytological features of acute myelogenous leukemia with 8; 21 chromosome translocation]. 192 Aug 38

In an attempt to detect residual leukemic cells during complete remission (CR), we used 4 monoclonal antibodies detecting markers at different stages of myeloid maturation. Bone marrow cells of AML patients at diagnosis/relapse or in CR were compared with normal controls at day 0 and 7, after incubation with colony stimulating factors, by the alkaline phosphatase/antialkaline phosphatase method. In AML patients at diagnosis/relapse, the expression of the early differentiation markers (CD34, HLA DR) was significantly increased and that of the late marker CD15 significantly decreased at day 0. After day 7 liquid cultures, the markers HLA DR and CD13 were significantly increased and CD15 significantly decreased. During CR a significant increase in day 7 liquid cultures of the markers HLA DR and CD13 was found compared to normal controls. These results may reflect the proliferation in culture of residual leukemic cells in CR patients.
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PMID:[Differentiation antigens on normal bone marrow cells and following culture with growth factors in patients with acute myeloid leukemia (AML)]. 194 59

Indirect immunofluorescence staining with monoclonal antibody (MoAb) CL203.4 of malignant cells from 269 patients with hematologic malignancies showed a heterogeneous expression of CD54/intercellular adhesion molecule-1 (ICAM-1). This marker was expressed by malignant cells of 57 out of 118 patients with myeloid malignancies and 69 out of 135 with B-lymphoid malignancies. On the other hand, CD54 was not detected on malignant cells of 16 patients with T-lymphoid malignancies. In myeloid malignancies, CD54 is preferentially expressed by "stem cell-derived" malignancies, being detectable on blast cells from almost all patients affected by chronic myelogenous leukemia in blast phase or myelodysplastic syndromes and by only 34% of patients with de novo acute myeloid leukemia (AML). The expression of CD54 did not correlate with any specific myeloid FAB subtype, although three cases of highly undifferentiated AML (FAB MO) displayed maximal levels of the antigen. The expression of CD54 in AML was significantly associated with that of CD34 and HLA-DR antigens. In B-lymphoid malignancies, CD54 expression appears to correlate with the differentiation stage of malignant cells, since B-origin acute lymphoblastic leukemias and conventional B-chronic lymphocytic leukemias (B-CLL; ie, "dim SIg" CLL) expressed lower levels of CD54 than more mature lymphoproliferative disorders ("bright SIg" CLL, prolymphocytic leukemias, and lymphoplasmacytic tumors). "High-grade" B-cell non-Hodgkin's lymphomas (B-NHL) express in general a higher level of CD54 than "low-grade" ones. This finding in conjunction with the expression of CD54 in all 17 patients with "bright SIg" CLL investigated (characterized by marked organomegaly and poor prognosis) suggest that the differential expression of CD54 in lymphoproliferative disorders may also relate to their degree of malignancy.
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PMID:Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders. 197 71

Translocations between chromosomes 8 and 21, t(8;21)(q22;q22), occur most commonly in acute myelogenous leukemia (AML) of the M2 FAB type. We studied two cases of acute leukemia with t(8;21) by immune phenotyping and IgH and T-cell receptor beta chain gene rearrangement analyses. These cases had increased blasts in bone marrow (greater than 50%). Auer rods, and evidence of granulocyte maturation. Blasts from both cases expressed CD19(B4), a B-cell antigen, as well as myeloid antigens including CD13(My7) and CD33(My9). HLA-DR, CD34, and TdT were also strongly positive. IgH or TCR beta gene rearrangements were not detected. We suggest that some cases of acute leukemia with t(8;21) may be hybrid leukemias with transformation in a multipotent stem cell.
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PMID:Are some cases of acute leukemia with t(8;21) hybrid leukemias? 217 2

Thirty-one cases of acute leukemia with blast cells greater than or equal to 70% positive for the hematopoietic stem cell Ag, CD34 (MY10, HPCA-1), were identified from the University of Nebraska Medical Center and The Johns Hopkins Oncology Center over an 18-month period. Fourteen of the cases were classified as early B-lineage ALL, 3 cases were other ALL subtypes, and 14 of the cases were ANLL. Five of the 17 cases of ALL expressed one or more myeloid-associated surface Ags, 3 ANLL cases expressed CD10 (CALLA, J5), and T-lymphoid Ags were present in 12 of 31 cases (1 T-cell ALL, 3 of 16 B-lineage ALL cases, and 8 of 14 ANLL cases). Eleven of 12 CD34+ ALL cases studied had abnormal karyotypes; only 7 of 12 CD34+ ANLL cases studied had abnormal karyotypes, and 3 of these were CD10+ ANLL. Six cases were Ph1 positive, including the one mature B cell ALL, 4 early B-lineage ALL, and 1 CD10+ ANLL case. Good and poor prognosis subgroups of high frequency of expression of CD34 leukemias could be identified, generally, as would have been predicted by previously defined criteria. Thus, of the 10 Ph1-negative early B-lineage ALL patients, 9 achieved CR (90%). At the other extreme, the CR rate of CD10- ANLL was 4 of 11 (36%). The leukemias characterized by greater than or equal to 70% of cells positive for CD34 form a relatively undifferentiated subset of the leukemias which may show features associated with more than one lineage, and if CD10- and myeloid morphology, may respond poorly to therapy.
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PMID:Acute leukemia expressing the normal human hematopoietic stem cell membrane glycoprotein CD34 (MY10). 245 68


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