Abstract
Disruption of Runx1/AML1 subnuclear localization, either by a single amino acid substitution or by a chromosomal translocation [e.g., t(8;21)], is linked to the etiology of acute myeloid leukemia (AML).Here, we show that this defect induces a select set of micro-RNAs (miR) in myeloid progenitor cells and AML patients with t(8;21).Both Runx1 and the t(8;21)-encoded AML1-ETO occupy the miR-24-23-27 locus and reciprocally control miR-24 transcription.miR-24 directly downregulates mitogen-activated protein kinase (MAPK) phosphatase-7 and enhances phosphorylation of both c-jun-NH2-kinase and p38 kinases.Ex pression of miR-24 stimulates myeloid cell growth, renders proliferation independent of interleukin-3, and blocks granulocytic differentiation. Thus, compromised Runx1 function induces a miR-dependent mechanism that, through MAPK signaling, enhances myeloid proliferation but blocks differentiation-key steps that contribute to leukemia.
Original language | English (US) |
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Pages (from-to) | 8249-8255 |
Number of pages | 7 |
Journal | Cancer research |
Volume | 69 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2009 |
ASJC Scopus subject areas
- Oncology
- Cancer Research