Journal
BLOOD
Volume 114, Issue 19, Pages 4169-4178Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-12-191619
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Funding
- Japan Society for the Promotion of Science
- US National Institutes of Health [R01 DK068348]
- Dutch Cancer Society and the Netherlands Organization for Scientific Research
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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. (Blood. 2009; 114:4169-4178)
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