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Blood. 2014 Apr 10;123(15):2412-5. doi: 10.1182/blood-2013-10-532374. Epub 2014 Mar 4.

Implications of the miR-10 family in chemotherapy response of NPM1-mutated AML.

Author information

1
Division of Hematology.

Abstract

Nucleophosmin-mutated acute myeloid leukemia (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Because miR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs could predict chemotherapy response in AML. We found that high baseline miR-10 family expression in 54 untreated cytogenetically heterogeneous AML patients was associated with achieving CR. However, when we included NPM1 mutation status in the multivariable model, there was a significant interaction effect between miR-10a-5p expression and NPM1 mutation status. Similar results were observed when using a second cohort of 183 cytogenetically normal older (age ≥ 60 years) AML patients. Loss- and gain-of-function experiments using miR-10a-5p in cell lines and primary blasts did not demonstrate any effect in apoptosis or cell proliferation at baseline or after chemotherapy. These data support a bystander role for the miR-10 family in NPM1mut-AML.

PMID:
24596420
PMCID:
PMC3983615
DOI:
10.1182/blood-2013-10-532374
[Indexed for MEDLINE]
Free PMC Article

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