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)

Micromegakaryocytes (MMK) were defined morphologically by the cell area, nucleus form and cytoplasmic structure. Bone marrow smears of 7,156 patients were retrospectively analyzed. MMK were found most frequently and abundantly in acute non-lymphatic leukaemia, chronic myeloid leukaemia and pre-leukaemia. The presence of more than 10% MMK in the megakaryocyte population suggest a pre-leukaemic condition or non-lymphatic leukaemia. The platelet production of MMK is probably quantitatively normal although a functional defect is suspected.
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PMID:Micromegakaryocytes in Human Bone Marrow. 677 70

Acute thrombocytopenia and megakaryocyte infection have been investigated during the preleukemic phase of the disease induced by the Rauscher murine leukemia virus (RMuLV) in mice. Injection of RMuLV, either intravenously or intraperitoneally, rapidly induced thrombocytopenia, possibly as a result of direct interaction between platelets and viral particles. The susceptibility to this acute thrombocytopenia was genetically controlled and was inherited as a dominant trait. Murine strains with H-2d or H-2k haplotype, which are susceptible to the induction of leukemia by RMuLV, developed thrombocytopenia, whereas leukemia-resistant H-2b and H-2q strains of mice failed to develop thrombocytopenia. Using B10 H-2-congenic and intra-H-2-recombinant mice, it was shown that the susceptibility to RMuLV-induced thrombocytopenia was controlled by gene(s) in or closely linked to the D region of the H-2 complex. Megakaryocytes may be one of the first sites for the replication of RMuLV. Indeed, among bone marrow cells, only megakaryocytes expressed viral antigens gp70 and p30 during the initial phase of RMuLV infection. In addition, megakaryocytes from infected mice were able to transfer preleukemic thrombocytopenia as well as leukemia in syngeneic mice. The infection of megakaryocytes by RMuLV appears to be genetically controlled in a manner similar to the induction of thrombocytopenia, since only the megakaryocytes from mice developing thrombocytopenia were infected by RMuLV. These results indicate that the gene(s) governing the induction of thrombocytopenia by RMuLV may be the same gene(s) (or closely linked to the gene) that controls the susceptibility to leukemogenesis, and would be consistent with the expression of the gene product, presumably a receptor-like molecule for RMuLV, on platelet and megakaryocyte membranes.
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PMID:Induction of acute thrombocytopenia and infection of megakaryocytes by Rauscher murine leukemia virus reflect the genetic susceptibility to leukemogenesis. 683 48

2 cases of megakaryocytic leukaemia are presented as a variant of myeloproliferative disorders. The uncontrolled proliferation of the megakaryocyte-platelet cell line occurred after splenectomy and treatment of blastic phase. Applicability of the term megakaryocytic leukaemia is discussed as well as its relationship to similar disorders. It is suggested that an extensive neoplastic proliferation of megakaryocytes with abnormal maturation and thereby formation of large dysplastic platelets in extramedullary organs especially the liver in the end stage of myelofibrosis is a possible mechanism for this disorder. Treatment with platelet-pheresis may be an effective part of therapy.
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PMID:Megakaryocytic leukaemia as a phase of myeloproliferative disorders. 720 Nov 56

Thrombocytopenia is a consistent feature of murine leukemia L5178Y. To define the mechanism(s) associated with the decrease in platelets, serial thrombokinetic studies were performed on various days after intravenous inoculation of 10(6) L5178Y ascites cells. At the nadir of thrombocytopenia (day 5), the recovery and circulating half-time of transfused normal 51Cr-platelets was only one half of control values. The loss of circulating radioactivity (70%) at 1 hr was accounted for by splenic (40%) and hepatic (30%) accumulation of labeled platelets. However, the liver contained three times more radioactivity per milligram of tissue than the spleen. There was no increase in hepatic accumulation of 59Fe-labeled red cells under the same conditions. When 51Cr-labeled leukemic platelets (day 3) were infused into normal animals, the circulating half-time was 50% of control. Despite spleen and liver enlargement, the blood volume of the leukemic mice did not increase. The megakaryocyte concentration remained unchanged after inoculation of leukemic cells, but the diameter of megakaryocytes increased significantly from days 5 to 10. These studies show that thrombocytopenia in mice transplanted with L5178Y leukemia occurs as a result of shortened platelet survival and increased organ sequestration. The increase in hepatic platelet accumulation suggests that the mechanism of thrombocytopenia is platelet specific and is not due to passive organ pooling.
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PMID:Altered platelet kinetics in thrombocytopenic mice with L5178Y leukemia. 741 65

Identification of megakaryocyte precursors with immunohistochemical methods in bone marrow trephine biopsy specimens (embedded in a plastic resin, Immuno-Bed) was performed from patients with blastic phase of chronic granulocytic leukaemia (five cases), from chronic megakaryocytic-granulocytic myelosis (four cases) and from acute megakaryoblastic leukaemia (11 cases). In megakaryoblasts of bone marrow biopsies immunohistochemical reactions using the ABC method and monoclonal antibodies against von Willebrand antigen and GpIIb/IIIa (CD41) were visible in various percentages depending on the maturation's degree of megakaryocyte precursors. The number of circulating blast cells determined by flow cytophotometry was nearly similar to those of observed in biopsies. The greatest bone marrow reticulin content could be detected in acute megakaryoblastic leukaemia cases. Despite the different clinicopathological entities, the presence of the same phenotype (megakaryoblasts) was associated with a short survival in these haematological malignancies (in CGL MKB phase 4.0, in CMGM MKB phase 4.2, and in AML M7 5.8 months, respectively).
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PMID:Megakaryocyte markers in myeloproliferative disorders. 750 75

In this report we describe four cases of acute megakaryocytic leukemia demonstrated by the presence of megakaryocyte-platelet-related cell-surface antigens. These were detected utilizing flow cytometry and monoclonal antibodies in addition to both platelet peroxidase activity, which was shown by ultrastractural cytochemistry, and emergence of differentiation antigens, while culturing these leukemic cells. The blasts of one patient possessed both platelet GpIb and GpIIb/IIIa cell-surface antigens detected by AN51(CD42b), J15, P2, and HPL2(CD41), respectively, whereas the remaining three patients almost completely lacked GpIb cell-surface antigen. Hence the former were diagnosed as immature(pro)megakaryocytic leukemia and the latter as acute megakaryoblastic leukemia from the viewpoint of immunophenotypic analysis. While we cultured these leukemic cells in conditioned medium prepared from phytohemagglutinin-stimulated leukocytes and interleukin 3, expression of CD36(OKM5) antigen (thrombospondin receptor) increased gradually according to the differentiation and maturation of these cells. Finally, all leukemic cells differentiated to mature megakaryocytes. The function of CD36 on these cells remains to be elucidated.
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PMID:Expression of the thrombospondin receptor (CD36) on the cell surface in megakaryoblastic and promegakaryocytic leukemias: increment of the receptor by megakaryocyte differentiation in vitro. 751 32

In this study, we evaluated the in vitro growth of normal hematopoietic progenitors (CFU-GM, BFU-E, CFU-GEMM, CFU-meg) stimulated by optimal sources of colony stimulating activity in the absence or presence of 10(-6) M all-trans retinoic acid (ATRA). ATRA alone did not show any colony-stimulating ability when added in culture to partially purified bone marrow populations. On the other hand, it significantly increased the number of CFU-GM (p = 0.003) and both the number (p = 0.009) and size (p = 0.002) of CFU-meg in the presence of appropriate colony-stimulating activity. Since ATRA had only modest stimulatory effects on purified CD34+ cells, the megakaryocyte colony-stimulating activity of ATRA was mainly due to an increased production of endogenous cytokines by bone marrow accessory cells. In parallel experiments, the in vitro growth of the different hematopoietic progenitors was evaluated in 28 patients affected by acute non-lymphoid leukemia (ANLL), mainly acute promyelocytic leukemia (APL). Bone marrow cells were harvested after remission induction obtained: (i) in ten APL patients treated with ATRA followed by one chemotherapy cycle (CHT) (3/7: Daunorubicin+Ara-C): group A ('ATRA/CHT'); (ii) eight APL patients treated with one CHT cycle alone (3/7 as above): group B ('APL-CHT'); (iii) in ten ANLL-non-APL patients after one CHT cycle (3/7 as above): group C ('ANLL-CHT'). The number of the different hematopoietic progenitors, and in particular CFU-GM and CFU-meg, was significantly higher in APL patients treated with ATRA plus CHT (group A) compared to APL (group B) or ANLL-non-APL (group C) patients treated with CHT alone (CFU-GM: p = 0.01; CFU-meg: p = 0.03). Our data demonstrate that ATRA is able to potentiate both normal and APL megakaryocytopoiesis and suggest that the in vivo administration of ATRA could be beneficial in other pathological conditions, where the megakaryocyte progenitor cell compartment is impaired.
Leukemia 1994 Dec
PMID:All-trans retinoic acid potentiates megakaryocyte colony formation: in vitro and in vivo effects after administration to acute promyelocytic leukemia patients. 752 59

Stem cell factor (SCF) is a cytokine for hematopoietic progenitor cells and plays an important role in megakaryocyte proliferation. The UT-7 cell line was established from a patient with megakaryoblastic leukemia, and its growth and survival are strictly dependent on interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), or IL-6. In this study, we showed that SCF also supported the growth of UT-7 in the absence of other cytokines and downregulated the cell surface c-kit receptors. Constitutive expression of SCF by introducing SCF expression vector made UT-7 grow factor-independently in liquid medium, but not in semisolid medium. This SCF-expressing factor-independent UT-7 (UT-7scf9) expressed the membrane bound form of SCF on their surface, but did not secrete detectable amounts of soluble SCF. UT-7scf9 formed aggregates as they grew in the absence of cytokines, and this aggregation was inhibited by adding soluble SCF into the medium. UT-7 cultured with SCF and UT-7scf9 cultured without cytokines expressed GM-CSF, and anti-GM-CSF neutralizing antibody partially inhibited their growth. These results suggest that SCF stimulated UT-7 proliferation partially through the autocrine-loop of GM-CSF, and UT-7scf9 expressed SCF mostly as a membrane-bound form, which transduces its growth signal through c-kit receptor as they aggregate by cell-to-cell interaction.
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PMID:Cell-to-cell interaction of cytokine-dependent myeloblastic line constitutively expressing membrane-bound stem cell factor abrogates cytokine dependency partially through granulocyte-macrophage colony-stimulating factor production. 753 35

The c-mpl proto-oncogene which encodes a member of the hematopoietic cytokine receptor superfamily has been recently shown to be the receptor for thrombopoietin (TPO), which stimulates megakaryocyte progenitor expansion and differentiation. We studied c-mpl expression by Northern blot analysis, in a large series of 58 MDS. No expression was found in 14 patients with refractory anemia (RA) or with refractory anemia with ring sideroblasts (RARS). In contrast 11/26 (42%) patients with refractory anemia with excess of blasts (RAEB), or with RAEB in transformation (RAEBt), and 8/18 (44%) patients with chronic myelomonocytic leukemia (CMML) expressed c-mpl. In CMML patients, no correlation was found between c-mpl expression and any prognostic factor tested, nor with the course of the disease. In contrast, in RAEB and RAEBt, expression of c-mpl was correlated with high Bournemouth scoring (P < 0.005) and poor survival (P = 0.02) due to leukemic transformation. Forty-five per cent (5/11) of the c-mpl positive patients evolved towards AML with a mean follow-up of 10.5 months, while 13% (2/15) of the c-mpl negative patients developed a secondary leukemia, with a mean follow-up of 21.1 months. Moreover, in RAEB and RAEBt, a significant correlation was observed between c-mpl, CD34, megakaryocyte glycoprotein IIb (GPIIb) expression, and the presence of dysmegakaryopoiesis. These results indicate that patients with RAEB and RAEBt, with high expression of the c-mpl, CD34, and GPIIb genes, may identify a subgroup of patients with particularly poor prognosis, due to an increased risk of secondary leukemia. More aggressive therapy could be justified in these patients.
Leukemia 1995 May
PMID:Prognostic value of c-mpl expression in myelodysplastic syndromes. 753 13

Infection of mice with the murine leukemia virus (LP-BM5) was evaluated as a model for the thrombocytopenia of HIV/AIDS. Percent 35S incorporation into platelets, platelet size, platelet count, platelet-associated immunoglobulins (PAIgG), and megakaryocyte size and number were evaluated over a period of 3-9 weeks postinfection (PI). Thrombopoietin from human embryonic kidney cells was administered to mice 9 weeks PI, and similar indices of platelet production were measured 2, 3, and 4 days after treatment with a biological preparation of thrombopoietin (thrombocytopoiesis-stimulating factor, or TSF). Platelet counts decreased in a time-dependent fashion (p = 0.0006) following infection, reaching a nadir at 8 weeks PI (82% of control values). Percent 35S incorporation into platelets also decreased over the 9-week period (p = 0.0001), falling to 63% of control values by week 9. Additionally, platelet volume increased in a linear fashion (p = 0.01), rising to 105% of control values by week 9. No changes in PAIgG were noted over the 9-week period. Megakaryocyte numbers in the femoral marrow were decreased at 8 weeks PI (p = 0.02, 78% of control values), while increased mean megakaryocyte size (p = 0.007, 116% of controls) was noted in the same animals. Increased numbers of naked megakaryocyte nuclei were observed at 3 weeks PI (p < 0.05, 208% of control values). Administration of 2 U/mouse of a highly purified preparation of TSF to virus-infected, thrombocytopenic mice resulted in increased thrombocytopoiesis, as compared to human serum albumin-treated, virus-infected controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of murine leukemia virus infection as a model for thrombocytopenia of HIV/AIDS: mechanism of thrombocytopenia and modulation of thrombocytopenia by thrombopoietin. 754 11


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