Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 6 (IL-6) is a multifunctional cytokine that also influences megakaryocyte (MK) development. To delineate the relationship between IL-6 and thrombopoietin (TPO), the putative physiological regulator of MK maturation, serum IL-6 levels and platelet counts were correlated in various clinical disorders. IL-6 was measured by a [3H] thymidine incorporation assay using the IL-6-dependent B9 cell line; 1 U is approximately equal to 1 pg/ml of a recombinant (r)IL-6 standard. Specificity of the assay was confirmed by neutralizing rIL-6 and selected sera containing IL-6 activity with anti-IL-6 antibody. Samples (n = 120) were obtained from normal individuals and patients with leukemia, myeloproliferative and rheumatologic disorders, solid tumors, and after bone marrow transplantation and chemotherapy. Patients were also grouped as to whether they had an ongoing inflammatory process, that is, an active infection, solid tumor malignancy, or rheumatological disorder. Serum IL-6 levels were 4.6 +/- 1.4 U/ml for normal individuals and ranged up to 14.8 x baseline; moderate increases (greater than 2 x normal) were found in 21.5% of all patients. Whereas only 39% of thrombocytopenic sera (less than 150,000 platelets) had elevated IL-6 levels, 91% of these sera were from patients with an ongoing inflammatory process. Only 29% of the thrombocytotic sera (greater than 400,000) had elevated IL-6 levels, but 86% of these sera were from patients suffering from concurrent inflammation. Overall, 80% of all patients with elevated serum IL-6 had definitive ongoing inflammatory processes. There was no inverse relationship between platelet numbers and IL-6 levels. Thus, the idea that IL-6 is TPO appears doubtful. However, production of IL-6 during inflammation may result in increased platelet numbers and account for the secondary thrombocytosis observed in some patients.
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PMID:Is interleukin 6 the physiological regulator of thrombopoiesis? 157 93

Peripheral blood leukemic cells from four patients with peroxidase negative acute leukemia, which expressed neither myeloid nor lymphoid cell surface antigens, were analyzed by using monoclonal antibodies (MoAb) capable of recognizing megakaryocyte-platelet-related antigens. Leukemic cells from one case reacted with 5F1 MoAb, whereas cells from all the tested cases reacted with OKM5 MoAb, which belongs to the same CD group as 5F1 (CD36). Also, culture cells from megakaryoblastic leukemia cell line, MEG-01, and human erythroleukemia cell line, HEL, showed a different pattern of expression for the CD36 antigen molecule detected by 5F1 and OKM5 MoAb, individually. Furthermore, we have demonstrated that the epitopes recognized by 5F1 and OKM5 MoAb appear on the same CD36 molecule on the surface of HEL cells by means of the two-color analysis using FACS-IV. On the basis of our experiments, we conclude that, CD36 molecule, a receptor for TSP, is synthesized and expressed in at least two ways, inside the cells and on the surface of megakaryocyte lineage leukemias and megakaryocytic leukemia cell lines MEG-01 and HEL. This is strongly suggestive that thrombospondin (TSP)-mediated adhesion represents an alternative pathway for cytoadherence, and that CD36 expression on various kinds of cells may lack some essential modifications or components necessary for the TSP receptor activity.
Leukemia 1990 Jul
PMID:Different expression of CD36 antigen molecule on the surface of megakaryocyte lineage leukemias and megakaryocyte leukemia cell lines MEG-01 and HEL. 169 6

Regulation of megakaryocyte and platelet production remains poorly understood. In culture system two separate activities are needed for maximum production of megakaryocyte progenitors: promotor of clonal expansion and promoter of maturation, other growth factors and cells also contribute to regulation of megakaryocytopoiesis. Increased proliferation of megakaryocytes is observed in myeloproliferative disorders and idiopathic thrombocytopenic purpura, and decreased proliferation is found in aplastic anaemia and hypomegakaryocytic thrombocytopenia. Dysmegakaryocytopoiesis is present in myelodysplastic syndromes and acute leukaemia, and a proliferation of immature megakaryocytes in acute megakaryoblastic leukaemia. Increased understanding of human megakaryocytopoiesis is beginning to help in rational clinical management.
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PMID:Human megakaryocytopoiesis--normal and abnormal. 169 25

MEG-01s, an established human megakaryoblastic leukemia cell line, exhibited specific high-affinity binding sites for [3H]iloprost, a stable prostaglandin (PG) I2 analogue, for [3H]SQ-29548, a stable thromboxane (TX) A2 antagonist and, for [3H]PGE2/PGE1, but not for [3H]PGD2. In the MEG-01s cells, iloprost/PGI2, or PGE1 stimulated cAMP production with ED50 values practically identical to the IC50 values for the [3H] iloprost binding. STA2 and U46619, TXA2/PGH2 agonists, PGE2/PGE1, iloprost/PGI2, and thrombin elevated the intracellular concentrations of Ca2+ ([Ca2+]i), as determined by Fura-2 fluorescence signals. Elevation of [Ca2+]i by PGE2/PGE1 and iloprost, but not that by TX-agonists or thrombin, was totally dependent on the presence of extracellular Ca2+. This effect by PGE2/PGE1 was partially inhibited by prior treatment of the cells with islet-activating protein (IAP), while that by TX-agonists or by PGI2/iloprost was not affected. We tentatively conclude from these results that: (1) MEG-01s cells express (a) PGI2/PGE1 receptor(s) coupled to adenylate cyclase and Ca2+ influx, a TXA2/PGH2 receptor coupled to the phosphatidylinositol-turnover-Ca2+ system, and the PGE2/PGE1 receptor coupled to Ca2+ influx; (2) the receptors for TXA2/PGH2 and iloprost and those for PGE2/PGE1 and thrombin are coupled to IAP-insensitive and IAP-sensitive GTP-binding proteins, respectively, and function in a different manner to elevate [Ca2+]i. Thus, the MEG-01s cell line is a pertinent model for studying eicosanoid receptor-mediated signal transduction in platelet/megakaryocyte systems.
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PMID:Characterization of prostaglandin and thromboxane receptors expressed on a megakaryoblastic leukemia cell line, MEG-01s. 171 95

The commitment process of a human megakaryoblastic cell line (MEG-O1) induced with phorbol ester, TPA, was investigated with special reference to glycoprotein (GP) IIb/IIIa expression, multinuclear formation, and DNA replication. TPA (10(-7) mol/L) completely inhibited cellular division in MEG-O1, but did not suppress de novo DNA synthesis. Two days' culture with 10(-7) mol/L TPA was sufficient for MEG-O1 cells to initiate an irreversible commitment process. These cells could not resume cell growth and expressed GP IIb/IIIa antigen; some of them showed multinuclear form and DNA polyploidy even after removal of TPA from the culture medium. DNA histogram analysis showed that, upon treatment with TPA, the percentage of cells whose DNA ploidy was more than 8N was 5 to 10 times higher than that of control cells. Precise analysis using cell size fractionation by centrifugal elutriation method showed that there was strong correlation between the percentage of multinuclear cells and DNA polyploidy in TPA-treated cells. The percentage and staining intensity of GP IIb/IIIa and other megakaryocytic phenotypes such as von Willebrand factor and PAS staining were highest in large multinuclear cell populations, suggesting that these cells are the most differentiated population in this system. In TPA-treated cells, the activity of DNA polymerase alpha, a marker for cell growth, remained at the same level as in control cells. Aphidicolin, a specific inhibitor of DNA polymerase alpha, completely inhibited the differentiation induction of MEG-O1 cells with TPA measured by either GP IIb/IIIa expression or multinuclear cell formation. Therefore, DNA replication appears to be involved in the process of phenotypic expression as well as endomitosis in megakaryocyte differentiation of MEG-O1 cells. Aphidicolin was also effective in inhibiting megakaryocytic differentiation of other leukemia cell lines such as human erythroleukemia (HEL) and K562 cell lines induced with TPA, suggesting the close interplay of DNA replication and phenotypic expression in megakaryopoiesis.
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PMID:Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1. 174 84

Hematopoietic growth factors (HGFs) interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) individually have been shown to increase the percentage of acute myeloid leukemia (AML) blasts in S phase and enhance the cytotoxic effects of Ara-C against these blasts in culture. We compared in vitro the effects of a combined treatment with GM-CSF (10 ng/mL) plus IL-3 (10 ng/mL) on the metabolism and cytotoxicity of Ara-C in normal bone marrow mononuclear cells (NBMMC) and AML blasts. NBMMC from six healthy volunteers and AML blasts from 10 patients were incubated for 20 hours with or without IL-3 plus GM-CSF, followed by a concurrent treatment with Ara-C for 4 additional hours. Exposure to the HGFs and Ara-C produced significantly higher intracellular Ara-CTP levels as well as higher Ara-CTP/dCTP pool ratios in AML blasts as compared with NBMMC. Treatment with HGFs resulted in [3H] Ara-C DNA incorporation that was significantly higher in AML blasts versus NBMMC. This selective improvement of Ara-C metabolism in AML blasts was associated with an enhanced Ara-C-mediated leukemia colony-forming unit (CFU) growth inhibition. In contrast, exposure to HGFs resulted in an improved colony growth of normal CFU granulocyte-monocyte and CFU-granulocyte, erythroid, monocyte, megakaryocyte. These in vitro studies indicate that a combined treatment with IL-3 plus GM-CSF may improve the selectivity of Ara-C against AML blasts.
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PMID:Treatment with interleukin-3 plus granulocyte-macrophage colony-stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts. 182 60

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and theta-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and beta-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.
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PMID:Establishment and characterization of a human leukemic cell line with megakaryocytic features: dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival. 182 23

To analyze the development pathways of early hematopoietic cells, we studied the rearrangement and expression of the immunoglobulin (Ig) and T-cell receptor (TCR) genes in 12 patients with acute unclassified leukemia (AUL). Leukemia cells from these patients were negative for myeloperoxidase staining and failed to express B-cell, T-cell, or megakaryocyte associated antigens. The expression of the CD7 antigen, myeloid associated antigens, or both was detected in three patients each. Ig and/or TCR gene rearrangements were detected in seven of the 12 patients, and five had rearrangement of both the Ig and TCR genes. Full length mature TCR gene transcripts were not demonstrated in most of the patients showing TCR gene rearrangements. In contrast, cells from two patients with germline configurations of the Ig and TCR genes tested expressed truncated forms of both Ig and TCR genes. These results suggest that AUL may generally originate from undifferentiated cells with an aberrant rearrangement and/or expression of the Ig and TCR genes.
Leukemia 1991 Apr
PMID:Acute unclassified leukemia originating from undifferentiated cells with the aberrant rearrangement and expression of immunoglobulin and T-cell receptor genes. 182 9

From 1982 to 1985, four cases of primary myelofibrosis were diagnosed in our department. Three were boys and one was a girl. Their ages ranged from 7 months to 15 years. The diagnosis was made based on anemia, leukoerythroblastic change and presence of giant platelets in the peripheral blood, and a bone marrow biopsy showing myelofibrosis. Most of them had anemia, fever, and hepatosplenomegaly on admission. The anemia was severe and refractory to repeated transfusions and steroid therapy in 3 out of the 4 cases. Splenectomy was performed in 1 case, but without satisfactory results. The clinical course and blood pictures in one case resembled leukemia of megakaryocyte lineage (M7), but results of marker studies of the blast cells ruled out the possibility of M7. Three of them underwent leukemic transformation within 2 years and died soon after. The other one died of sepsis 2 weeks after diagnosis. Myelofibrosis in childhood occurs rarely, however, when it does, it always runs a rapid and fatal course.
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PMID:Primary myelofibrosis in children: report of 4 cases. 198 Dec 37

A 61-year-old man with Philadelphia chromosome-positive chronic myelogenous leukemia developed megakaryoblastic leukemia. In the blast phase, his blast cells showed undifferentiated megakaryoblastic characteristics with no alpha-granules or demarcation membranes but with detectable platelet peroxidase (PPO) activity and surface glycoprotein (GP) IIb/IIIa. The patient has remained reasonably well for at least 12 months after blastic crisis, and 6-mercaptopurine alone has been effective in controlling leukocytosis and megakaryoblast proliferation. The expression of mRNA for platelet-specific proteins, such as GPIIb and platelet factor 4 (PF4), was studied in the patient's blast cells by the Northern blot analysis. Both GPIIb and PF4 mRNA were detected in the blast cells. Cytoplasmic maturation occurs later than the synthesis of the surface GP during megakaryocyte maturation. Therefore, PF4 mRNA expression should be a marker of mature megakaryoblasts. The PF4 mRNA expression in megakaryoblastic leukemia may indicate that a patient will have long survival and a good response to chemotherapy.
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PMID:Platelet factor 4 mRNA expression in cells from a patient with megakaryoblastic crisis of chronic myelogenous leukemia. 199 Dec 66


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