A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 Acute Lymphocytic Leukemia cells
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Author(s)
Kotani, Ai
Ha, Daon
Schotte, Diana
den Boer, Monique L.
Armstrong, Scott A.
Lodish, Harvey F
Date Issued
March 2010
Journal
Cell Cycle
Publisher
Landes Bioscience
Citation
Kotani, Ai et al. “A Novel Mutation in the miR-128b Gene Reduces miRNA Processing and Leads to Glucocorticoid Resistance of MLL-AF4 Acute Lymphocytic Leukemia Cells.” Cell Cycle 9.6 (2010): 1037–1042. Web.
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Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.4161/cc.9.6.11011
