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

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4169-4178
Number of pages10
JournalBlood
Volume114
Issue number19
DOIs
StatePublished - Nov 5 2009

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