miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

Ai Kotani, Daon Ha, James Hsieh, Prakash K Rao, Diana Schotte, Monique L den Boer, Scott A Armstrong, Harvey F Lodish

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

Originele taal-2Engels
Pagina's (van-tot)4169-78
Aantal pagina's10
TijdschriftBlood
Volume114
Nummer van het tijdschrift19
DOI's
StatusGepubliceerd - 5 nov. 2009
Extern gepubliceerdJa

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