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)

Four monoclonal antibodies against human erythrocyte membrane antigens were established. The antigenic determinants of KOR-E1, E3, E6 were Pr1h antigen, Wrb antigen, and the trypsin sensitive portion of glycophorin A (EnaTS) respectively. The antigen recognized by KOR-E4 could not be determined. The reactivities of these antibodies with normal hematopoietic cells, malignant hematopoietic cell lines (N = 31), and fresh leukemic cells obtained from 128 patients with various types of leukemias were studied. All antibodies reacted only with erythrocytes among peripheral blood cells, and also KOR-E6 reacted only with erythroid cells among bone marrow cells. KOR-E3 had no reactivity with any cell lines examined, and KOR-E1 and KOR-E4 were reactive with some lymphoid cell lines. However, KOR-E6 had specific reactivities with erythroid (HEL, K562), megakaryocytic (CMK-1), multiphenotypic (KOPM-28), and basophilic (KU-812) cell lines. The antigen (glycophorin A) recognized by KOR-E6 was expressed on a small population of mononuclear cells separated from acute lymphoblastic leukemia (3/70), acute myelogenous leukemia (2/12), monosomy 7-myeloproliferative disorder (1/1), juvenile CML (1/1), and transient myeloproliferative disorder with Down's syndrome (4/12), although it could not be determined whether these cells were leukemic cells or not. KOR-E6 was reactive with a large population of leukemic blasts in erythroleukemia (2/2) and acute megakaryoblastic leukemia (3/6). Thus, KOR-E6 appears to be an erythroid marker of leukemic cells.
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PMID:[Monoclonal antibodies against human erythrocyte membrane antigens and their reactivities with hematopoietic cells]. 261 36

Recently, a human megakaryoblastic cell line, CMK, was established from the peripheral blood of a megakaryoblastic leukemia patient with Down syndrome. Using this cell line, we studied the proliferation and differentiation of megakaryocytic cells in the presence of highly purified human hematopoietic factors and phorbol 12-myristate-13-acetate (PMA). In a methylcellulose culture system, interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitated colony formation by CMK cells in a dose-dependent manner. The maximum stimulating doses of these factors were 10 and 200 U/mL, respectively. These concentrations were comparable to those that stimulate activity in normal hematopoietic cells. In contrast, granulocyte-colony stimulating factor (G-CSF), macrophage-colony stimulating factor (M-CSF), and erythropoietin (EPO) had no effects on the colony formation of CMK cells. In a liquid culture system, 20% of the CMK cells expressed glycoprotein IIb/IIIa (GPIIb/IIIa) antigen without hematopoietic factors, whereas 40% of the cells expressed GPIIb/IIIa with the addition of IL-3 and GM-CSF. EPO also slightly enhanced expression of GPIIb/IIIa. On the other hand, PMA inhibited growth of CMK cells and induced most of them to express the GPIIb/IIIa antigen. Furthermore, PMA induced CMK cells to produce growth activity toward new inocula of CMK cells. This growth factor (GF) contained colony-stimulating activity (CSA) in normal bone marrow (BM) cells. The activity was believed to be attributable mainly to GM-CSF, since 64% of this activity was neutralized by anti-GM-CSF antibodies and a transcript of GM-CSF was detected in mRNA from PMA-treated CMK cells by Northern blot analysis. These observations suggest that GM-CSF, as well as IL-3, should play an important role in megakaryocytopoiesis.
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PMID:Growth and differentiation of a human megakaryoblastic cell line, CMK. 266 39

In the present study, we examined the effect of prostaglandin E1 (PGE1) on Ca2+ mobilization in a human megakaryocyte (the progenitor of platelets) leukemia cell line, designated as CMK. PGE1 caused a rapid and dose-dependent increase in the intracellular free calcium level ([Ca2+]i) associated with the elevation of cyclic AMP. The PGE1-induced elevation of [Ca2+]i was decreased by the prior addition of ethylene glycol bis(2-aminoethylether)tetraacetic acid to the medium by approximately 25% of the control. This result indicates that the PGE1-induced elevation of [Ca2+]i is due to influx of Ca2+ from the external medium and to mobilization of Ca2+ from intracellular stores. Pretreatment of CMK cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulus for protein kinase C, further enhanced the PGE1-induced increase in the cellular cyclic AMP level. Inversely, pretreatment of CMK cells with TPA (10 nM), prior to the addition of PGE1, inhibited the PGE1-induced elevation of [Ca2+]i. Dibutyryl cyclic AMP and forskolin did not elevate [Ca2+]i or affect the PGE1-induced Ca2+ mobilization. The inhibitory action of TPA in the PGE1-induced elevation of [Ca2+]i was mimicked by other protein kinase C-activating agents, such as 1-oleoyl-2-acetylglycerol and N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, and was selectively restored by protein kinase C inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride. Thus, the inhibitory modulation of TPA on the PGE1-induced elevation of [Ca2+]i is mediated through protein kinase C activation. PGE1 had no inductional effect of megakaryocytic phenotypic changes in CMK cells. The biological role of PGE1, which increased [Ca2+]i and cyclic AMP levels in the CMK cells, remains to be determined.
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PMID:Elevation of intracellular calcium ion by prostaglandin E1 and its inhibition by protein kinase C in a human megakaryocyte leukemia cell line. 273 22

A functional cDNA for the human prostacyclin receptor was isolated from a cDNA library of CMK cells, a human megakaryocytic leukaemia cell line. The cDNA encodes a protein consisting of 386 amino acid residues with seven putative transmembrane domains and a deduced molecular weight of 40,956. [3H]Iloprost specifically bound to the membrane of CHO cells stably expressing the cDNA with a Kd of 3.3 nM. This binding was displaced by unlabelled prostanoids in the order of iloprost = cicaprost >> carbacyclin > prostaglandin E1 (PGE1) > STA2. PGE2, PGD2 and PGF 2 alpha did not inhibit it. Iloprost in a concentration-dependent manner increased the cAMP level and generated inositol trisphosphate in these cells, indicating that this human receptor can couple to multiple signal transduction pathways.
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PMID:Cloning and expression of a cDNA for the human prostacyclin receptor. 751 39

The proto-oncogene, c-kit, encodes a transmembrane tyrosine kinase receptor (KIT) and plays an important role in haemopoiesis. We have identified a 95 kD soluble form of KIT (S-KIT) in culture supernatant of human megakaryoblastic cell line, CMK. To study the physiological significance of S-KIT, we have established a sensitive sandwich ELISA system. Serum samples from healthy individuals contained detectable amounts of S-KIT. Next, we determined a total of 220 samples from 134 patients with haemopoietic disorders. A considerable number of patients with acute myeloid leukaemia (AML), especially those with more immature phenotypes (M0, M1 or M2) had elevated levels of serum S-KIT. Those levels decreased to the normal range after effective chemotherapy. In chronic myeloid leukaemia, patients with myeloid blastic crisis showed markedly elevated levels of serum S-KIT. In contrast, S-KIT levels decreased in cases with either acute or chronic lymphoid leukaemia. There was a tendency for patients with severe aplastic anaemia to show decreased levels, but it was not significant. In myelodysplastic syndrome, S-KIT levels appeared to vary by subsets, with higher concentration in more advanced forms of the disease. Although the functional role of S-KIT is not yet elucidated, these results suggest that the serum S-KIT levels may reflect the pathological states of various haematological disorders.
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PMID:Soluble c-kit molecule in serum from healthy individuals and patients with haemopoietic disorders. 757 39

c-mpl is the receptor for the recently identified megakaryocyte growth and differentiation factor thrombopoietin. Thrombopoietin has been shown to be capable of raising platelet counts in animals and is about to enter clinical trials in humans. In anticipation of its likely use in the care of patients receiving cancer chemotherapy, we evaluated the expression of human c-mpl by reverse transcription PCR on 39 human cell lines and 20 primary human tissue samples derived from both normal and malignant sources. c-mpl transcripts were found in all megakaryocytic cell lines tested (CMK, CMK-2B, CMK-2D, SO, and DAMI), the CD34+ leukemia cell line KMT-2, and a hepatocellular carcinoma cell line (Hep3B). Among primary tissues, fetal liver cells and brain had detectable levels of c-mpl message, and among primary tumors, none were found to express c-mpl. These data support the conclusion that c-mpl has restricted expression that is primarily, but not exclusively, related to megakaryocytopoiesis. These observations suggest that thrombopoietin is unlikely to have direct effects on other malignant or normal tissue should it have a clinical role in the treatment of chemotherapy-induced thrombocytopenia.
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PMID:Thrombopoietin receptor expression in human cancer cell lines and primary tissues. 762 56

A human cDNA encoding a putative G protein-coupled receptor designated chemokine beta receptor-like 1 (CMKBRL1) was isolated from an eosinophilic leukemia library. Its deduced sequence is approximately 40% identical to previously cloned receptors for the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), which are chemoattractants for blood leukocytes, and is 83% identical to the product of the orphan rat cDNA RBS 11. Like the MIP-1 alpha/RANTES receptor, CMK-BRL1 is encoded by a small, single-copy gene that maps to chromosome 3p21 and is expressed in leukocytes. However, two screening assays with a broad panel of chemokines failed to identify its ligand. CMKBRL1 mRNA was detectable by Northern blot hybridization in neutrophils and monocytes, but not eosinophils, and was also found in eight solid organs that were tested with particularly high expression in brain. The RNA distribution of the known beta chemokine receptors was overlapping but distinct from that of CMKBRL1. MIP-1 alpha/RANTES receptor mRNA was detectable in neutrophils, monocytes, eosinophils, and in all eight solid organs tested, with particularly high expression in placenta, lung, and liver. MCP-1 receptor mRNA was found in monocytes, lung, liver, and pancreas. These results suggest that the ligand for the putative CMKBRL1 receptor is a beta chemokine that targets both neutrophils and monocytes. Moreover, the RNA distributions suggest that CMKBRL1, the MIP-1 alpha/RANTES receptor, and the MCP-1 receptor may have both overlapping and distinct biological roles.
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PMID:Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene. 764 14

We investigated the expression of three platelet alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fbg), in a human megakaryocytic cell line (CMK 11-5) by immunocytochemical staining, using the alkaline phosphatase anti-alkaline phosphatase (APAAP) complex method and immunoelectron microscopy of ultrathin-frozen sections. CMK 11-5, established from a Down's syndrome patient with acute megakaryoblastic leukemia, has characteristics closely resembling those of normal megakaryocytes. Under basal conditions, TSP expression was observed in the alpha-granules, whereas the other two proteins were not detected. When the cells were cultured with 12-o-tetradecanoylphorbol-13-acetate (TPA), the expression of TSP was enhanced and vWF was also detected, but not Fbg. Cells cultured in the presence of plasma for 24 h took up Fbg and stored it in their alpha-granules. These findings suggest that TSP and vWF are synthesized by CMK 11-5 cells, with the former being produced more rapidly than the latter, whereas Fbg is endocytosed from the plasma.
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PMID:Expression of platelet alpha-granule proteins in a human megakaryocytic leukemia cell line (CMK 11-5). 769 24

CAMAL (common antigen of myelogenous acute leukemia) is an antigenic preparation isolated in this laboratory from the bone marrow or peripheral blood leucocytes of persons with myeloid leukemias. Material from CAMAL preparations, which migrates in the range of 30 to 35 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE, P30-35 CAMAL), was shown to exert an inhibitory effect on in vitro colony formation by progenitor cells from normal healthy donors. The same preparations of P30-35 CAMAL, in contrast, exerted a stimulatory effect on in vitro colony formation by progenitor cells from patients with chronic myelogenous leukemia (CML). We now report that both the inhibitory effect on normal colony formation and the stimulatory effect on CML colony formation mediated by P30-35 CAMAL were blocked using phenyl methyl sulfonyl fluoride (PMSF), an inhibitor of the activity of serine proteases. Similarly, both the P30-35 CAMAL-mediated inhibitory effect on normal colony formation and the P30-35 CAMAL-mediated stimulatory effect on CML colony formation were blocked using the peptide ala-pro-phe-CMK, also an inhibitor of serine protease activity. These results suggest the involvement of proteolytic activity, either directly or indirectly, in the alterations of in vitro myelopoiesis exerted by P30-35 CAMAL.
Leukemia 1994 Apr
PMID:Reversal of CAMAL-mediated alterations of normal and leukemic in vitro myelopoiesis using inhibitors of proteolytic activity. 815 56

To study the involvement of cyclins in cell-cycle progression, changes of mRNA levels for three G1 cyclins (cyclin C, D1 and E) and cyclin A were studied in a leukemia cell line, HEL cells, before and after incubation with 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, the cyclin D1 mRNA level markedly increased in the HEL cells when the cells were growth-arrested by TPA, while the amounts of cyclin E and A mRNAs decreased to an almost undetectable level in HEL cells after incubation with TPA. The similar marked increment of the cyclin D1 mRNA level was observed in other leukemia cell lines, CMK and HL-60 cells, after incubation with TPA. The cyclin C mRNA was not detected in HEL cells before and after incubation with TPA.
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PMID:Increment of the cyclin D1 mRNA level in TPA-treated three human myeloid leukemia cell lines: HEL, CMK and HL-60 cells. 837 83


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