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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 2-year-old girl with a very rare form of acute megakaryoblastic leukemia (AMKL), having the 11p13;14q11 translocation specific for T-cell malignancies, is reported. She was diagnosed as having AMKL on the basis of her bone marrow, which contained 30% megakaryoblasts identified by characteristic morphology on May-Giemsa stain, positive for platelet peroxidase activity and for the surface marker of platelet glycoprotein IIb/IIIa, CD41. Cytogenetic studies of marrow cells revealed 47,XX,i(7q), +der(11)t(11;14)(p13;q11), -14, +21. She achieved hematologic remission after two courses of chemotherapy including behenoyl cytarabine, acracinorubicin, 6 mercaptopurine, and prednisolone, but soon relapsed and died 11 months after admission. This case suggests that adequate diagnostic assessments of morphology, surface markers, and cytogenetics are necessary for proper diagnosis in leukemia and lymphoma, and that an important, though as-yet unidentified, gene in megakaryopoiesis may reside in the 14q11 chromosomal region.
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PMID:A t(11;14)(p13;q11) specific for T-cell malignancies in acute megakaryoblastic leukemia. 765 3

We have established a novel human megakaryoblastic cell line, designated as MEG-A2, from a patient with megakaryoblastic crisis of Philadelphia (Ph) chromosome positive chronic myelogenous leukemia. MEG-A2 cells showed positive phenotypes for periodic acid Schiff and alpha-naphthylbutyrate esterase reactions, but were negative for myeloperoxidase and naphthol ASD chloroacetate esterase reactions. Flow cytometric analyses of cell surface markers revealed that MEG-A2 cells had a low level of GP IIb/IIIa expression as well as apparent expressions of CD4, CD7, CD13, CD33 and CD34 antigens, but no expression of GP Ib nor glycophorin A. Stimulation with phorbol 12-myristate 13-acetate (PMA) dramatically increased the expression of megakaryocyte-related markers such as HPL-3, J15, Pit-1, Y2/51 and AN51 in MEG-A2 cells. The PMA-stimulation also induced expression of platelet peroxidase (PPO) in MEG-A2 cells on electromicroscopic observation. Proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or erythropoietin were observed, and the expression of GP IIb/IIIa was increased by stimulation with GM-CSF, IL-3, erythropoietin and interleukin-6 (IL-6). Protein S mRNA expression was seen in cultured cells on Northern blot analysis. Expression of platelet factor 4 mRNA was induced in PMA-stimulated cells, and a marked accumulation of protein was observed in the culture medium. In conclusion, a new cell line, MEG-A2, belongs to the relatively immature megakaryocytic lineage and has markedly increased megakaryocytic characteristics with PMA stimulation.
Leukemia 1995 Feb
PMID:Establishment and characterization of an immature human megakaryoblastic cell line, MEG-A2. 786 73

This review summarizes the changes in cell surface antigen expression during proliferation and differentiation of human erythroid progenitors. The content is based on our experimental data obtained from complement-mediated cytotoxicity assays against hematopoietic progenitors and a combined technique of sequential micromanipulations of paired daughter cells derived from erythroid burst-forming units (BFU-E) and immunostaining with a panel of monoclonal antibodies, as well as from current information. BFU-E has CD34, CD41a (platelet glycoprotein[GP]IIb/IIIa) and CD41b(GPIIb) antigens. Paired daughter cells derived from BFU-E have CD41a, CD41b, CD71 (transferrin receptor) and HLA-DR antigens, but not CD34 or CD33 antigen. The CD36 antigen (thrombospondin receptor or GPIV) is first expressed on the cells after 5 days of culture, in agreement with the report that the anti-CD36 positive fraction contained a greater part of the erythroid colony-forming units (CFU-E). The blood group A antigen is first expressed on cells from aggregates derived from BFU-E after 5 days of culture. Glycophorin A is expressed on cell surface after 7 days of culture when proerythroblasts first appear. Hemoglobin alpha is expressed after 8 days of culture and coincides with the first appearance of basophilic erythroblasts. This review provides useful information on the identification of leukemic cells from poorly differentiated acute leukemias such as early erythroblastic leukemia and acute megakaryoblastic leukemia, and is useful in the understanding of the commitment and differentiation of erythroid and megakaryocytic progenitors in normal hematopoiesis.
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PMID:Cell surface antigen expression in human erythroid progenitors: erythroid and megakaryocytic markers. 806 85

We report a successful ereated case of acute megakaryoblastic leukemia (AMKL) with myelofibrosis (MF), which achieved a disease free condition, with disappearance of MF, for over 24 months after allogeneic bone marrow transplantation (BMT) and summarized cases of MF receiving BMT reported in Japan to evaluate the influence of MF on engraftment of bone marrow (BM). A 40-year-old man was admitted on Jan. 29, 1991 due to anemia and thrombocytopenia. BM aspiration resulted in a dry tap and MF and cells stained positive with anti-GPIIb/IIIa (CD41a) antibody were demonstrated by BM the biopsy specimen. Complete remission was achieved by multi-drug chemotherapy including behenoylcytosine arabinoside, etoposide, mitoxantrone and prednisolone (PLS). After preconditioning with little BU+CY, BMT was performed from an HLA-identical brother on Jan. 16, 1992. From day 9 of post BMT, acute skin graft versus host disease (grade 1) was observed, which was controlled by 60 mg/day of PSL. Engraftment was achieved on day 12. Although cystitis developed, he was discharged on Apr. 5, 1992 and remains disease free. Including the present case, seven allogeneic BMT patient with MF have been reported so far in Japan. Four cases in whom MF recovered before BMT showed better results than other three cases that still showed MF at BMT. Reversal of MF seems to be a favorable pre-transplant factor for successful BMT in patients with MF.
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PMID:[Reversal of myelofibrosis is an important pre-transplant factor for bone marrow grafting--a successful case of allogeneic bone marrow transplantation for an acute megakaryoblastic leukemia]. 813 12

A 25-year-old man noted swelling of the right cervical lymph nodes in October 1983. Diagnosis of malignant lymphoma was made on the basis of pathological examination of biopsies. Despite both chemotherapy and irradiation treatment, blast cells appeared in the peripheral blood and bone marrow in April 1984. Immunophenotypic analysis demonstrated that the blasts in the patient's peripheral blood expressed CD13, CD33, CD41a, and no markers for T or B lymphocytes, suggesting that he had been suffering from megakaryocytic sarcoma. We established a new cell line derived from the blasts in the peripheral blood, designated KH184. KH184 cells expressed glycoprotein (GP) Ib (CD42b) and GPIIb/IIIa (CD41a), while platelet peroxidase (PPO) activity was negative in an ultrastructural study. Both Northern blot and flow cytometric analysis of surface antigens and DNA content revealed that treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) did not induce the maturation of these cells. Various cytokines such as interleukin 3 (IL-3), interleukin 6 (IL-6), and leukemia inhibitory factor (LIF) had no effect in promoting the growth of KH184 cells. KH184 cells expressing CD41a seem to possess unusual characteristics. KH184 cells, human GPIIb- and GPIIIa-positive leukemia cells, which lack response to TPA-induced differentiation, provide a new and unique model for the characterization of factors that are implicated in the terminal differentiation of megakaryocytes, and should aid in studies of the mechanism underlying the occurrence of megakaryocytic sarcoma.
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PMID:Extramedullary tumor as presentation of leukemia: establishment of a new human GPIIb- and GPIIIa-positive leukemia cell line. 816 81

A human megakaryoblastic leukemia cell line, HIMeg, was established recently. Previous studies have shown that retinoic acid (RA) and 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] have potent effects on the proliferation and differentiation of HIMeg cells. Recently, the effect of dexamethasone (Dex), a synthetic glucocorticoid, on HIMeg cell growth and differentiation was examined in comparison with RA and sex steroid hormones. It was observed that in a methylcellulose culture system, Dex suppressed the clonal proliferation of HIMeg cells in a dose-dependent manner. The inhibitory effects of Dex could be reversed by RU486, a potent glucocorticoid antagonist. In contrast, sex steroid hormones had little effect on the clonal proliferation of HIMeg cells. In a liquid culture system, only 2% of HIMeg cells expressed glycoprotein IIb/IIIa (GPIIb/IIIa) antigen without hormone treatment, whereas 45% and 30% of the cells expressed GPIIb/IIIa following the addition of RA and Dex, respectively. To examine the molecular basis of the hormone-induced cell differentiation, glucocorticoid receptor (GR) expression was studied by Scatchard analysis. It was shown that there existed a saturable, high-affinity GR in HIMeg cells and the GR number was altered after Dex or RA treatment of the cells, suggesting that the cellular effects of glucocorticoids on HIMeg cells were mediated by GR.
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PMID:Glucocorticoid-induced growth inhibition and differentiation of a human megakaryoblastic leukemia cell line: involvement of glucocorticoid receptor. 840 Dec 54

The distribution of the major platelet membrane glycoproteins (GP), Ib, IX, IIb-IIIa and IV (or CD36), which play important roles as receptors for adhesive molecules in haemostasis and thrombosis, was studied in 34 patients with myeloproliferative disorders (MPD): 13 had essential thrombocythaemia (ET), 12 had polycythaemia vera (PV) and nine had chronic myelogenous leukaemia (CML). Only occasionally were modifications of the numbers of GPIb or GPIIb-IIIa measured using the binding of specific radiolabelled antibodies to platelets. In contrast, 2-3-fold increases of the total CD36 content and the surface CD36 expression were measured in almost all patients studied, using a radioimmunoassay and the direct binding of the radiolabelled antibody, FA6-152, to the platelet surface, respectively. These results indicate that the abnormality affected both the external and internal CD36 pools. Therefore platelet CD36 may be a useful tool for the diagnosis and the follow-up of MPD patients. Surface CD36 has been proposed as a platelet receptor for thrombospondin, an adhesive glycoprotein that is released from platelets upon activation and promotes aggregate formation. Despite a 2-fold increase of CD36 molecules, resting and thrombin-activated platelets from ET patients expressed the same amount of thrombospondin as normal platelets, suggesting that there is not a direct correlation between the CD36 expression and thrombospondin binding either spontaneously or after activation.
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PMID:Increased platelet CD36 constitutes a common marker in myeloproliferative disorders. 855 64

Megakaryocytic cell lines, established from the blood of patients with leukaemia, provide us with a unique opportunity to study the proliferation, differentiation and maturation of megakaryocytes. Eighteen human and three animal cell lines that express some megakaryocytic features have been described in the literature. Many of these cell lines have primitive multiphenotypic properties of erythroid, myeloid and megakaryocytic cells, while some show more restricted megakaryocyte-specific markers. The most consistent cell marker of megakaryocytic cell lines is the presence of platelet membrane glycoprotein (GPIIb-IIIa) in human cell lines and that of acetylcholinesterase in mouse or rat cell lines. The expressions of GPIb, von Willebrand factor and platelet peroxidase are variable among different cell lines, perhaps reflecting different stages of differentiation or a neoplastic nature of immortal cell lines. Treatment of many of these cell lines with phorbol esters leads to enhanced expression of the megakaryocytic programme.
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PMID:Megakaryocytic cell lines. 915 15

Thrombopoietin (Tpo) is a cytokine which stimulates megakaryocyte maturation. We found that Tpo is constitutively and ubiquitously expressed in all tissues examined, including bone marrow stromal cells, even in thrombocytopenia, thrombosis and steady-state condition in mice. Thus, platelet level in circulation is not regulated by Tpo gene expression. Furthermore, when the purified megakaryocytes were cocultured with the stromal cells, most of the megakaryocytes adhered to the stromal cells and remained unchanged, while free megakaryocytes induced proplatelet formation. Thus the stromal cells in bone marrow secrete Tpo and stimulate megakaryocytopoiesis, but the interaction of megakaryocytes with the stromal cells may suppress platelet formation. Study on signal transduction through Mp1 revealed that Tpo induces activation of JAK2 and Tyk2, which in turn activate STAT1, STAT3 and STAT5. Further, Tpo stimulates transcription factors GATA-1 and NF-E2, which induce differentiation markers, GPIIb/IIIa and Pm-1. In addition, Shc, Vav, Ras, Raf-1, MAPKK, MAPK and Pim-1 are also activated. Thus, Tpo activates a lineage-specific cascade as well as a specific JAK-STAT cascade and a common signaling cascade.
Leukemia 1997 Apr
PMID:Regulation of megakaryocytopoiesis by thrombopoietin and stromal cells. 920 16

The CD9 antigen, a major platelet glycoprotein, is a member of the tetraspan superfamily. We show that treatment of K562 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) which induces megakaryocytic differentiation, leads to a seven-fold increase in CD9 expression, which becomes associated with the integrin beta1, suggesting that it is functionally relevant. The upregulation of CD9 expression precedes the appearance of the megakaryocytic-specific marker GPIIb (CD41) as well as integrins beta3 (GPIIIa/CD61), alpha v (CD51) and VLA-2 (CD49b). Both GPIIb/IIIa expression and CD9 upregulation are dependent on protein kinase C (PKC) activation since they are blocked by the specific inhibitor GF109203X. Steady-state levels of CD9 and GPIIb mRNA were also measured by quantitative RT-PCR. Both messengers were detected on resting cells and were shown to accumulate during TPA treatment. However, the increase of the CD9 mRNA was detected much earlier than the increase of GPIIb mRNA (1-2 h vs 24-48 h). Using different constructs of the 5'-flanking domain of the CD9 gene cloned ahead of the CAT reporter gene, we could demonstrate that a responsive element was located in a 52 bp fragment of the promoter of the CD9 gene. Altogether, these data suggest that CD9 upregulation in the megakaryocytic lineage could occur at early stages of differentiation.
Leukemia 1997 Aug
PMID:Upregulation of CD9 expression during TPA treatment of K562 cells. 926 83


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