Research ArticleCancer

Intronic miR-3151 Within BAALC Drives Leukemogenesis by Deregulating the TP53 Pathway

Sci. Signal.  15 Apr 2014:
Vol. 7, Issue 321, pp. ra36
DOI: 10.1126/scisignal.2004762

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Resolving an Oncogenic Genomic Mystery

The BAALC locus is associated with poor prognosis in a subset of acute myeloid leukemia patients, but the prognosis appears to correlate best with the production of both miR-3151, a microRNA encoded within an intron of this gene, and the BAALC transcript. Eisfeld et al. found that the abundance of miR-3151 altered the expression of genes associated with the tumor suppressor p53 pathway and that the p53-encoding transcript contained a functional miR-3151–binding site. In leukemia cell lines and in mice injected with cells engineered to express high amounts of miR-3151, the abundance of miR-3151 correlated with resistance to apoptosis and more severe disease, respectively. Transcription start sites with distinct transcription factor regulation may explain the discordant production of the two products of this locus in cancer patients.