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

作者：Kotani Ai; Ha Daon; Schotte Diana; den Boer Monique L; Armstrong Scott A; Lodish Harvey F^*

来源：Cell Cycle, 2010, 9(6): 1037-1042.

DOI：10.4161/cc.9.6.11011

• miRNA
• processing
• mutation
• steroid resistance
• miR-128

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.

• 出版日期2010-3-15
• 单位河北医科大学