A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells

Ai Kotani, Daon Ha, Diana Schotte, Monique L den Boer, Scott A Armstrong, Harvey F Lodish

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

MLL-AF4 acute lymphocytic leukemia has a poor prognosis, and the mechanisms by which these leukemias develop are not understood despite intensive research based on well-known concepts and methods. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate expression of target mRNA transcripts. We recently reported that ectopic expression of miR-128b together with miR-221, two of the miRNAs downregulated in MLL-AF4 ALL, restores glucocorticoid resistance through downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11). Here we report the identification of new mutations in miR-128b in RS4;11 cells, derived from MLL-AF4 ALL patient. One novel mutation significantly reduces the processing of miR-128b. Finally, this base change occurs in a primary MLL-AF4 ALL sample as an acquired mutation. These results demonstrate that the novel mutation in miR-128b in MLL-AF4 ALL alters the processing of miR-128b and that the resultant downregulation of mature miR-128b contributes to glucocorticoid resistance through the failure to downregulate the fusion oncogenes.

Originele taal-2Engels
Pagina's (van-tot)1037-42
Aantal pagina's6
TijdschriftCell cycle (Georgetown, Tex.)
Volume9
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 15 mrt. 2010
Extern gepubliceerdJa

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