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)

Megakaryocytes are the bone marrow cells that generate platelets. They are relatively rare cells, comprising between 0.03 and 0.06% of all nucleated marrow cells (R. L. Berkow et al., J. Lab. Clin. Med., 103: 811-818, 1984). The study of human megakaryocyte differentiation and function has been hampered by the small number of these cells available for study. Recently we have established a human cell line (EST-IU) from the marrow of a patient with an acute nonlymphocytic leukemia and a mediastinal germ cell tumor. While this cell line seems to express many of the phenotypic characteristics of human megakaryocytes, it does not appear to express any phenotypic properties associated with cells of the erythroid, lymphoid, granulocytic, or monocytic lineages. Transmission electron microscopy demonstrates frequent multinucleated cells. Staining for platelet peroxidase reactivity revealed darkening of the perinuclear envelope and the endoplasmic reticulum, a characteristic of cells of the megakaryocytic lineage. Indirect immunofluorescence assays reveal that EST-IU expresses reactivity with anti-platelet glycoprotein antisera, anti-Factor VIII-related antigen antisera, anti-Factor V antisera, anti-thrombocyte antisera, Tab (monoclonal anti-platelet glycoprotein IIb-IIIa), and anti-fibronectin antisera. Flow cytometry-derived DNA histograms demonstrate populations with multiple ploidies, ranging from approximately 4N to 32N. Based upon morphological and histochemical characteristics, antigenic expression, and nuclear characteristics, EST-IU cells appear to have a phenotype that closely resembles human megakaryocytes. This cell line should be useful in the further cell study of the molecular and cell biology of human megakaryocytopoiesis.
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PMID:Establishment in long term culture of megakaryocytic leukemia cells (EST-IU) from the marrow of a patient with leukemia and a mediastinal germ cell neoplasm. 300 22

The clonogenic growth of myeloid leukemia cell lines was inhibited by recombinant tumor necrosis factor (rTNF) at 1-15 pM concentration. However, wild type (promyelocytic) HL-60 cells were highly resistant to growth inhibition, but responded with differentiation into monocyte-like cells at 100 pM rTNF. The clonogenic growth of fresh acute myeloid leukemia cells was inhibited by 50% at approximately 15 pM rTNF. The growth of normal granulocyte-macrophage progenitors (CFU-GM) was also inhibited (by 50 pM rTNF), as was the growth of erythroid progenitors (BFU-E) (by 150 pM rTNF). A synergistic antiproliferative effect was demonstrated between rTNF and recombinant interferon-gamma. Use of radioiodinated rTNF enabled us to detect 1,500-2,100 binding sites on myeloid cell lines at 4 degrees C with Kd of approximately 300 pM. At 37 degrees C, the transfer of bound ligand to lysosomes was followed by degradation, inhibited by NH4+. No correlation was observed between the number of binding sites or affinity at 4 degrees C and antiproliferative response to the addition of rTNF.
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PMID:Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro. Relationship to cell surface receptor. 302 50

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.
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PMID:Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia. 304 49

Eight cases each of erythroleukemia (AML-M6) and erythroblastic crisis of chronic granulocytic leukemia (CGLBC-E) were immunophenotyped with the help of a panel of lineage-associated monoclonal antibodies (McAbs). The latter included those reactive with erythroid progenitor (BFU-E and CFU-E) and erythroid precursors at different stages of maturation. In six of eight cases of AML-M6, erythroblasts revealed an immature phenotype, as evident from reactivity of the blast cells with McAbs directed against the earlier stages of erythroid maturation. One case had the phenotype of CFU-E, and in the remaining case of AML-M6 the erythroblasts showed a "mature" surface antigenic profile. This immunophenotypic spectrum was unrelated to the morphologic maturity of the erythroblasts. In two cases of CGLBC-E, an early erythroblastic phenotype was observed, while in as many cases a "mature" phenotype was present. Four of eight cases, however, revealed a mixed, erythroid plus myeloid phenotype. In one of the four cases, two separate blast populations, which represented erythroblasts and myeloblasts, could be identified. In the remaining three cases the blasts were morphologically homogeneous and undifferentiated. High incidence of HLA-DR positivity in the latter three cases suggests the primitive nature of blasts cells and their closeness to the putative "bipotent" myeloid stem cell. Our study has shown phenotypic heterogeneity of blast cells in AML-M6 and CGLBC-E.
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PMID:Phenotypic heterogeneity of erythroblasts in erythroblastic leukemia revealed by monoclonal antibodies. 305 43

The influences of human tumor necrosis factor (TNF) (LuKII), recombinant human TNF-alpha, natural human interferon-gamma (HuIFN-gamma), recombinant HuIFN-gamma, and natural HuIFN-alpha were evaluated alone or in combination for their effects in vitro on colony formation by human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5% CO2 in lowered (5%) O2 tension. TNF (LuKII) and recombinant TNF-alpha caused a similar dose-dependent inhibition of colony formation from CFU-GM, BFU-E, and CFU-GEMM. Day 7 CFU-GM colonies were more sensitive than both day 14 CFU-GM colonies and day 7 CFU-GM clusters to inhibition by TNF. BFU-E colonies and CFU-GEMM colonies were least sensitive to inhibition with TNF. The suppressive effects of TNF (LuKII) and recombinant TNF-alpha were inactivated respectively with hetero-anti-human TNF (LuKII) and monoclonal anti-recombinant human TNF-alpha. The hetero-anti-TNF (LuKII) did not inactivate the suppressive effects of TNF-alpha and the monoclonal anti-recombinant TNF-alpha did not inactivate TNF (LuKII). The suppressive effects of TNF did not appear to be mediated via endogenous T lymphocytes and/or monocytes in the bone marrow preparation, and a pulse exposure of marrow cells with TNF for 60 min resulted in maximal or near maximal inhibition when compared with cells left with TNF for the full culture incubation period. A degree of species specificity was noted in that human TNF were more active against human marrow CFU-GM colonies than against mouse marrow CFU-GM colonies. Samples of bone marrow from patients with non-remission myeloid leukemia were set up in the CFU-GM assay and formed the characteristic abnormal growth pattern of large numbers of small sized clusters. These cluster-forming cells were more sensitive to inhibition by TNF than were the CFU-GM colonies and clusters grown from the bone marrow of normal donors. The sensitivity to TNF of colony formation by CFU-GM of patients with acute myelogenous leukemia in partial or complete remission was comparable with that of normal donors. When combinations of TNF and HuIFN were evaluated together, it was noted that TNF (LuKII) or recombinant TNF synergized with natural or recombinant HuIFN-gamma, but not with HuIFN-alpha, to suppress colony formation of CFU-GM, BFU-E, and CFU-GEMM from bone marrow of normal donors at concentrations that had no suppressive effects when molecules were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The suppressive influences of human tumor necrosis factors on bone marrow hematopoietic progenitor cells from normal donors and patients with leukemia: synergism of tumor necrosis factor and interferon-gamma. 308 33

Protein markers are often used to corroborate the morphological subtyping of hematopoietic malignancy. Most commonly, surface markers are used for the phenotyping of hematopoietic cells; however, internal proteins have also been used as markers. Glycophorin, hemoglobin A, hemoglobin F, and transferrin have all been used as markers for the erythroid phenotype. We have recently shown that carbonic anhydrase is constitutively and aberrantly expressed in two erythroleukemic cell lines. We here show that it is also present in high levels in primary erythroleukemic blasts and that it is a useful marker for the M6 phenotype when classifying acute nonlymphocytic leukemia.
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PMID:Carbonic anhydrase: a marker for the erythroid phenotype in acute nonlymphocytic leukemia. 308 39

In this report we present data on the expression of IL2 receptors on chronic phase CML cells. Using an anti IL2 receptor monoclonal antibody (McAb aIL2r) in indirect immunofluorescence we found significant proportions (42.2% +/- 19.7 SD) of the CML cells (previously depleted of E rosetting T cells) to be IL2 receptor positive following incubation in suspension for 18 hours at 37 degrees C. Noninduced cells did not express IL2 receptors. After induction the aIL2r positive and negative cell subpopulations were sorted and analyzed separately for morphology, lineage specific cell surface markers, and clonogenic cell numbers. The IL2 receptor positive CML subpopulations mainly contained blast cells and monocytes and revealed reactivity with myeloid McAbs but not with T cell, B cell, platelet, or erythroid markers. Clonogenic cells (CFU-GEMM, BFUe, and CFU-GM) were selectively recovered from aIL2r positive CML cells and thus were IL2 receptor positive. The addition of recombinant IL2 (rIL2) to CFU-GM and BFUe cultures, in concentrations from 50 to 500 U/mL, did not influence the efficiency of colony formation. Binding of a radiolabeled IL2 preparation to the in vitro activated CML cells indicated the presence of low affinity receptors for IL2. In contrast to CML, normal human marrow cells were consistently aIL2r nonreactive. Thus, IL2 receptor inducibility is a characteristic feature of CML clonogenic cells, which they share with AML, but not with normal marrow progenitors. The role of IL2 receptors in the regulation of proliferation of CML cells requires further investigation.
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PMID:Membrane receptors for interleukin 2 on hematopoietic precursors in chronic myeloid leukemia. 310 14

Bone marrow scintigraphy with indium chloride (111In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1. in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2. in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3. in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4. four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5. in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific.
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PMID:[Bone marrow scintigraphy with 111In-chloride--a clinical value for the hematological diseases]. 314 26

Immunophenotyping of acute nonlymphocytic leukemia has confirmed previous observations on the heterogeneity of this disease. The lack of leukemia-specific monoclonal antibodies as well as antibodies reactive with early myeloid cells is reflected in poor correlation of morphologically and cytochemically defined FAB classes with the immunophenotype of the leukemic cells. Possible exceptions are the microgranular variant of FAB-M3, megakaryocytic leukemia (FAB-M7), and early erythroid leukemias (FAB-M6). The use of antibody panels can alleviate the differential diagnosis of acute lymphoid and myeloid leukemias, especially those occurring in infants, and the discrimination of FAB-L2 and FAB-M1. Also, the immunophenotyping of presumptive hybrid leukemias can help to resolve the many questions about these leukemias with a particularly poor prognosis. The challenge for multiinstitutional groups is to define those clinically relevant subgroups of acute nonlymphocytic leukemia in children that have general acceptance and could provide the basis for new treatment strategies.
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PMID:Heterogeneity among the acute nonlymphocytic leukemias: value of immunophenotype for diagnosis, prognosis, and therapy. 315 47

Bone marrow and peripheral blood findings at the time of complete remission were analyzed in 333 patients with acute myelogenous leukemia to determine if any variables were predictive for remission duration and survival. Patients were categorized as to percentage of blasts, promyelocytes, erythroid precursors and lymphocytes in the marrow and hemoglobin concentration, leukocyte and platelet counts, and percentage of granulocytes and blasts in the blood. Additionally, the degree of cellularity in the marrow aspirate and biopsy were analyzed. Patients with less than 1% blasts in the marrow had significantly longer remission durations than those with blasts greater than or equal to 1% (P less than 0.01). Those with hypercellular marrows had significantly shorter remission (P less than 0.05) and survival (P less than 0.01). The transient presence of more than 3% blasts in the blood also was suggestive of a shorter remission duration and survival. The presence of less than 1% blasts in the marrow, normal or decreased biopsy cellularity, and no anemia at the time of remission defined a "good" prognostic group. The quality of remission should be assessed in evaluating the results of therapy and assigning further treatment.
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PMID:Prognostic significance of blood and marrow findings in acute myelogenous leukemia in remission. A Southeastern Cancer Study Group report. 316 56


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