MIR15A
Overview
MIR15A (MicroRNA 15a) is a tumor-suppressor microRNA located at chromosome 13q14.3 within the minimal deleted region (Mdr) of the 13q14 locus. Loss of MIR15A and its genomic neighbors DLEU1 and DLEU2 is a defining event in chronic lymphocytic leukemia (CLL) pathogenesis.
Alterations observed in the corpus
- Component of the minimal deleted region (Mdr) of 13q14 (together with DLEU1 and DLEU2); Mdr loss alone gives low-penetrance CLL in mouse models but cooperates with SF3B1 mutation for full disease acceleration and poor outcome PMID:26200345
Cancer types (linked)
- Chronic lymphocytic leukemia (CLL/SLL): del(13q14) including MIR15A is a defining cooperating lesion; Mdr loss synergizes with SF3B1-K700E mutation to accelerate CLL development and activate mTORC1/MYC signaling PMID:26200345
Co-occurrence and mutual exclusivity
- Co-occurs with SF3B1 mutation (K700E) in the aggressive double-mutant (DM) CLL subtype; SF3B1-mut / del(13q) co-occurrence associated with shorter time to first therapy independent of del(13q) alone, and inferior OS PMID:26200345
Therapeutic relevance
- The SF3B1-mut / del(13q) double-mutant CLL subtype (which includes MIR15A loss) provides mechanistic rationale for combining H3B-8800 (SF3B1-directed splicing modulator) with temsirolimus (mTORC1 inhibitor); combination was preferentially active on patient cells with both lesions PMID:26200345
Open questions
- The specific contribution of MIR15A loss (versus DLEU1/DLEU2) to mTOR pathway activation in the SF3B1-mut context is not separately dissected; Mdr was modeled as a unit in the murine system PMID:26200345
Sources
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