Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various compounds which modulated the intracellular signal transduction on the induction of class I major histocompatibility complex (MHC) antigens by recombinant human interferon-gamma (rIFN-gamma) were investigated using K562, chronic myelogenous leukemia cells. Class I or class II MHC antigens were not expressed in untreated K562 cells and rIFN-gamma (600 units/ml) weakly induced class I antigens on the cells. Among the compounds tested, verapamil but not the calcium ionophore A23187 enhanced the rIFN-gamma-induced class I antigen expression at both the surface molecule and mRNA levels and enhancement by verapamil occurred in a dose-dependent manner at non-toxic concentrations examined (approximately 50 microM). Verapamil alone had no inducible effect on MHC antigen expression. Deprivation of Ca2+ in culture medium by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) could not cause an enhancement of class I antigen induction by rIFN-gamma. Simultaneous exposure of K562 cells to rIFN-gamma (600 units/ml) and recombinant human tumor necrosis factor (rTNF; 1000 units/ml) in combination with verapamil (50 microM) resulted in a further increase of class I antigens in the cells. The expressions of c-myc oncogene in K562 cells were not changed when the cells were treated with rIFN-gamma (600 units/ml) or verapamil (50 microM), either alone or in combination. These results indicate that verapamil synergistically interacts with rIFN-gamma on the class I antigen induction in K562 cells irrespective of c-myc gene expression and that class I antigen induction in this cell line may not be relevant to calcium influx triggered by IFN-gamma.
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PMID:Effect of verapamil on the class I major histocompatibility complex antigen expression in K562 chronic myelogenous leukemia cells treated with recombinant human interferon-gamma. 151 24

Homoharringtonine (HHT) is a new drug with antileukemic activity which is currently tested for treatment of acute and chronic leukemias, either alone or in combination with other agents. Since HHT showed a low efficacy in refractory and relapsed acute leukemia and in the blastic phase of chronic myeloid leukemia (CML) which are frequently characterized by an overexpresion of the multidrug resistance (MDR)-related P170-glycoprotein, we postulated a relationship between the poor antileukemic effect of HHT in these leukemias and the expression of P170-glycoprotein. For this reason, sensitive (LOVO109 and CEM) and MDR (LOVO DX and CEM VLB) cell lines were exposed to HHT with or without some MDR modifiers, namely, Cyclosporine A (CyA), the Cyclosporine derivative SDZ PSC 833 (PSC), and the D-isomer of Verapamil (DVRP). It was found that MDR cells were about 15 times more resistant to HHT than non-MDR cells, and that resistance to HHT was significantly decreased by all the MDR modifiers that were tested. This in vitro study showed that HHT belongs to the category of MDR-related drugs, like anthracyclines, vinca alkaloids, epipodophylline derivatives, and taxol.
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PMID:MDR-related P170-glycoprotein modulates cytotoxic activity of homoharringtonine. 788 49