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

Using array technology that allows the simultaneous detection of gene expression of hundreds of genes, four patients with chronic myeloid leukemia (CML) were investigated at diagnosis and after starting administration of hydroxyurea. To detect the gene expression of peripheral blood mononuclears and granulocytes Human Cancer cDNA Array (CLONTECH) with 588 gene probes was used. Gene expression mononuclear and granulocyte profiles of patients at diagnosis were compared with the control profiles. The significant expression changes observed in most patients seemed to be important. Increased expression of c-jun N-terminal kinase 2 (JNK2), integrin alpha E, MMP-8, MMP-9 was detected in both fractions of most patients. In some samples PCNA, HDGF, MAPK p38, CD59 increased expressions were found. Significant down-regulation of expression in patients was detected in genes CDK4 inhibitor A, PURA, notch1 in mononuclears; STAT2, STAT5, RAR-alpha, MCL-1, junB, caspase 4 in granulocytes; CDK6, GADD153, ERBB-3, cadherin 5 in both fractions. Expression profiles detected in patients at diagnosis did not differ markedly from those after one-week treatment with hydroxyurea. Only in a few genes were significant changes after hydroxyurea administration observed and inter-individual expression differences were rather common.
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PMID:Gene expression profiling in chronic myeloid leukemia patients treated with hydroxyurea. 1215 98

Glycogen synthase kinase (GSK)-3beta may modulate endoplasmic reticulum (ER) stress-induced apoptosis; however, the mechanism remains unclear. Our data showed that human monocytic leukemia/lymphoma U937 and acute myeloid leukemia HL-60, but not chronic myeloid leukemia K562, cells were susceptible to apoptosis induced by ER stressor tunicamycin, a protein glycosylation inhibitor. Tunicamycin caused early activation of caspase-2, -3, -4, and -8, followed by apoptosis, whereas caspase-9 was slowly activated. Inhibiting caspase-2 reduced activation of caspase-8 and -3 but had no effect on caspase-4. Tunicamycin induced apoptosis independently of the mitochondrial pathway but caused lysosomal destabilization followed by lysosomal membrane permeabilization (LMP), cathepsin B relocation from lysosomes to the cytosol, and caspase-8 and -3 activation. It is notable that caspase-2 mediated lysosomal destabilization. Inhibiting GSK-3beta comprehensively reduced lysosomal apoptosis after caspase-2 inhibition. Unlike U937 and HL-60 cells, K562 cells showed nonresponsive ER stress and failure of activation of GSK-3beta and caspase-2 in response to tunicamycin. Activating GSK-3beta caused K562 cells to be susceptible to tunicamycin-induced apoptosis. Taken together, we show that GSK-3beta exhibits a mechanism of ER stress-induced lysosomal apoptosis in leukemia involving caspase-2-induced LMP and cathepsin B relocation, which result in caspase-8 and -3 activation.
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PMID:Glycogen synthase kinase-3beta mediates endoplasmic reticulum stress-induced lysosomal apoptosis in leukemia. 1918 82