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• W2007633189 abstract "Abstract Aberrant micro RNA (miRNA) expression has been described in human malignancies including B-cell lymphomas. We here report BCR-ABL– and c-MYC–dependent regulation of miRNA expression in chronic myeloid leukemia (CML) using microarray analysis (miCHIP) and miRNA-specific quantitative real-time reverse transcriptase–polymerase chain reaction (miR-qRT-PCR). In 3 bcr-abl–positive cell lines, expression of miRNAs encoded within the polycistronic miR-17-92 cluster is specifically down-regulated (2- to 5-fold) by both imatinib treatment and anti–BCR-ABL RNA interference (RNAi). In addition, anti–c-MYC RNAi reduces miR-17-92 expression in K562 cells in which miRNAs can specifically repress reporter gene expression, as demonstrated by specific miRNA inhibition with antagomirs. Furthermore, lentivirus-mediated overexpression of polycistronic miRNAs in K562 cells confers increased proliferation, partial resistance against anti–c-MYC RNAi, and enhanced sensitivity to imatinib-induced cell death. Finally, we determined miR-17-92 expression in purified normal (n = 4), early chronic-phase (CP) (n = 24), and blast-crisis (BC) (n = 7) CML CD34+ cells and found up-regulation of polycistronic pri-miRNA transcripts in CML and mature miRNAs in CP but not in BC CML. These data are in accordance with a BCR-ABL–c-MYC–miR-17-92 pathway that mediates enhanced miRNA expression in CP but not BC CML CD34+ cells. Altered miRNA expression may contribute to the pathophysiology of the disease and may provide potential targets for therapeutic intervention." @default.
• W2007633189 created "2016-06-24" @default.
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• W2007633189 date "2007-02-06" @default.
• W2007633189 modified "2023-10-15" @default.
• W2007633189 title "Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells" @default.
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• W2007633189 doi "https://doi.org/10.1182/blood-2006-09-045104" @default.
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