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

Nucleophosmin mutated AML (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Since 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. Pretreatment miRNA expression was analyzed in 54 de novo adult AML patients obtained from the MD Anderson Cancer Center Leukemia Tissue Bank (LTB) using the Ohio State University (OSU) miRNA microarray (ver.3).