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

K-sam/bek, N-sam/flg and FGFR3/sam3 establish gene family of the receptors for heparin-binding growth factors (HBGFs) or FGFs. These mRNAs were detected in human leukemia cells, CMK, K562 and HEL, which have megakaryocytic phenotype or the potency to differentiate into megakaryocytic lineage. In CMK cells N-sam/flg transcript level was enhanced by the culture with 12-O-tetradecanoylphorbol-13-acetate (TPA). cDNA-polymerase chain reaction identified K-sam/bek mRNA in human platelets, suggesting the involvement of HBGFs in megakaryocytopoiesis and functions of platelets.
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PMID:Expression of the heparin-binding growth factor receptor genes in human megakaryocytic leukemia cells. 131 27

Recombinant human tumor necrosis factor-alpha (TNF-alpha) was found to stimulate the growth of CMK, a human megakaryoblastic leukemia cell line. This stimulatory effect of TNF-alpha was blocked by anti-TNF-alpha antibody, but antibodies to recombinant human interleukin 3, granulocyte-macrophage colony-stimulating factor and interleukin 6 (all growth factors for CMK cells) did not reduce the stimulatory effect of TNF-alpha. Scatchard analysis showed that CMK cells expressed TNF-alpha receptors on the cell surface. The growth of CMK cells was also stimulated by lymphotoxin, which shares the same receptor as TNF-alpha. These results suggest that TNF-alpha stimulated the growth of CMK cells directly via its specific receptor.
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PMID:Stimulatory effect of tumor necrosis factor-alpha on the growth of CMK, a human megakaryoblastic leukemia cell line. 131 36

The CMK cell line is an acute megakaryoblastic leukemia cell line established from a patient with Down's syndrome, and is known to possess characteristics of normal megakaryocytes. Several cytokines with the ability to stimulate megakaryopoiesis, such as interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulated colony formation by CMK cells. The present study revealed that tumor necrosis factor-alpha (TNF-alpha) stimulated colony formation by CMK cells; the potency was almost equal to that of IL-3, IL-6 or GM-CSF. Scatchard plot analysis revealed that CMK cells possess two types of specific binding sites for TNF-alpha. The high-affinity binding sites had an affinity constant of 0.18 nM, and numbered 5,000. The low-affinity binding sites had an affinity constant of 1.8 nM and numbered 19,000. These results raise the possibility that TNF-alpha can act as a growth-stimulating agent on megakaryocyte-lineage cell line.
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PMID:Tumor necrosis factor-alpha stimulates colony formation by a megakaryoblastic leukemia cell line, CMK. 142 11

The short segments of cDNA encoding glycoprotein (GP)Ib alpha, GPIIb, GPIIIa and platelet factor (PF) 4 were amplified using reverse transcriptase-polymerase chain reaction (RT-PCR) in order to characterize various types of megakaryoblasts. Cell lines with megakaryocytic features (K562, CMK and HEL) were tested. GPIb alpha, GPIIb and GPIIIa mRNAs were found to be present in K562, CMK and HEL cells, while only HEL cells expressed PF4 or mRNA. These results suggested that megakaryoblastic cell lines could be categorized into two groups, one with the PF4 transcript and the other without it. PF4 mRNA was present in the cells obtained from one Down's syndrome patient with transient myeloproliferative disorder and in one patient with primary myelofibrosis and megakaryoblastosis. On the other hand, one patient with acute megakaryoblastic leukemia transformed from refractory anemia had a poor prognosis with megakaryoblastic leukemia cells which expressed no PF4 mRNA. These observations suggested that the expression of PF4 mRNA in peripheral blood megakaryoblasts may indicate the absence of a true leukemic process.
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PMID:Detection of platelet-specific protein mRNAs in different megakaryoblasts using the reverse transcriptase polymerase chain reaction. 149 50

smg p21A and -B (smg p21s) are ras p21-like small GTP-binding proteins (G proteins) with the same putative effector domain as ras p21s. Both smg p21A mRNA and smg p21B mRNA were detected in CMK, a human megakaryocytic leukemia cell line, and their levels were markedly elevated by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which caused the differentiation of this cell line into more mature megakaryocytes. The smg p21 protein molecules also increased during the TPA-induced differentiation of CMK cells. The mRNA level of glycoprotein IIb (GPIIb), a typical marker of the megakaryocytes, was increased by this treatment, but the time course of the increase in the smg p21 mRNA levels as more rapid than that of the increase in the GPIIb mRNA level. Ha-ras p21 mRNA was undetectable, but both Ki- and N-ras p21 mRNAs were detected in CMK cells and their levels were also increased during TPA-induced differentiation of CMK cells, although to a lesser extent than those of smg p21 mRNAs. Protein kinase C inhibitors inhibited the basal and TPA-induced smg p21A mRNA level, but cyclic AMP-elevating prostaglandin E1 or Ca(2+)-mobilizing ionomycin did not inhibit them. Cycloheximide enhanced the basal and TPA-induced smg p21A mRNA levels. Actinomycin D blocked the TPA-induced smg p21A mRNA levels, but showed no detectable effect on the elevated smg p21A mRNA level which was induced by pretreatment with TPA. A dramatic increase in the smg p21 mRNA levels was also observed in other leukemia cell lines during TPA-induced differentiation. These results suggest that TPA stimulated expression of the smg p21A gene, presumably through the action of protein kinase C at the transcriptional level rather than at the post-transcriptional level, in hematopoietic leukemia cells.
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PMID:Induction of smg p21/rap1A p21/krev-1 p21 gene expression during phorbol ester-induced differentiation of a human megakaryocytic leukemia cell line. 154 53

CMK is a human cell line derived from a megakaryoblastic leukaemia. It has characteristics of the megakaryocytic lineage, such as the presence of platelet peroxidase, membrane glycoproteins (GP)Ib and GPIIb/IIIa, alpha-granules, and demarcation membranes. The cell line proliferates autonomously in serum-containing medium. Here we report that the cell line expresses the gene for IL-6 and releases small quantities of the cytokine into the medium. Addition of exogenous IL-6 to cultures seeded into medium was found to promote growth of the cells. Conversely, addition of a neutralizing anti-IL-6 antibody inhibited cell growth. These data support the notion that autocrine IL-6 is one of the factors accounting for autonomous growth of the cell line.
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PMID:Interleukin 6, a possible autocrine growth and differentiation factor for the human megakaryocytic cell line, CMK. 199 94

Using the megakaryocytic leukemia cell lines, K-562 and CMK established from a Down's patient with acute megakaryoblastic leukemia, we studied the changes of antigen expression, cytosolic Ca2+ mobilization, thromboxane (TX) A2 formation and gene expression during megakaryocyte differentiation. We found that thrombospondin synthesis and platelet factor (PF)-4 gene expression were specific for mature megakaryoblasts, whereas collagen unresponsiveness and prostaglandin E1-induced Ca2+ mobilization were noted in immature megakaryoblasts alone. This experiment shows that functional and genetic analysis are useful for characterizing the leukemic megakaryoblastic cells. We analyzed the clinical, hematologic and genetic features of 4 patients with M7, and acute megakaryoblastic transformation of CML, MDS and essential thrombocythemia. In two patients, prednisolone and 6-MP were effective in cytoreduction. In 3 patients with increased platelet counts, normal CFU-Meg formation, the megakaryoblasts with platelet production, or the coexistence of immature megakaryoblasts with mature megakaryocytes were observed, thus indicating that some megakaryoblastic leukemia cells still have the capacity of differentiation. One patient had megakaryoblastic cells with PF-4 gene expression. These clinical findings suggest that the megakaryoblastic leukemia could not be characterized as usual leukemia and a more sensitive marker is required to differentiate leukemic megakaryoblasts from normal megakaryoblasts.
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PMID:[Megakaryocytic leukemia cell lines and megakaryocytic leukemia]. 238 Oct 77

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.
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PMID:A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20. 251 73

A new megakaryoblastic cell line (CMK), which also exhibits erythroid and myeloid markers, was established from a Down's syndrome patient suffering from acute megakaryoblastic leukaemia. The CMK cells were found to be positive in reactions with anti-platelet antibodies (anti-glycoproteins IIb/IIIa and Ib, and Plt-1). Platelet peroxidase (PPO) reactivity was found to be associated with the nuclear envelope and the endoplasmic reticulum but not with the Golgi apparatus. Some cells possessed cytoplasmic granules with the characteristics of alpha-granules and demarcation membranes. Karyotyping revealed near-tetraploidy (modal chromosome number of 95; ranging 87-98) and a translocation der(17)t(11;17), also found in the original leukaemic cells, confirming that the cells were derived from the patient's malignant blasts. The CMK cells were also found to be positive in reaction with anti-glycophorin A antibody, as well as with anti-myeloid antibodies (MY4, MY7 and MY9). Treatment of CMK cells with phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) greatly enhanced the reactivity with anti-platelet antibodies, increased the number of cells in which cytoplasm was dissociated into numerous segments and suppressed the reactivity with anti-glycophorin A. The proliferation of CMK cells was stimulated by interleukin-3 (IL-3) and granulocyte-macrophage colony stimulation factor (GM-CSF). This cell line should be a useful tool for analysing the basis of the afferent association between megakaryoblastic leukaemia and Down's syndrome, as well as for further study of megakaryocytic differentiation.
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PMID:Establishment of a human leukaemic cell line (CMK) with megakaryocytic characteristics from a Down's syndrome patient with acute megakaryoblastic leukaemia. 252 57

Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)-resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab')2 form [MRK16-F(ab')2], which recognizes P-glycoprotein (P-gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16-F(ab')2 reacted with four cell lines, K562/ADM, KYO-1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP-16) and actinomycin-D (ACT-D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 microM verapamil in vitro. Significant expression of mRNA of P-gp gene was also detected in K562/ADM, KYO-1 and HEL. MRK16-F(ab')2 did not react with 36 other cell lines. Among them, three cell lines, PL-21, P31/FUJ and KOPM-28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP-16, but not to vinca alkaloids or ACT-D. The level of ADM-resistance in these cell lines did not decrease significantly in the presence of 10 microM verapamil. Five cell lines, ATL-1K, HL-60, KMOE-2, ML-1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16-F(ab')2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.
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PMID:Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16. 257 8


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