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

Violaine Havelange, Parvathi Ranganathan, Susan Geyer, Deedra Nicolet, Xiaomeng Huang, Xueyan Yu, Stefano Volinia, Steven M. Kornblau, Michael Andreeff, Carlo M. Croce, Guido Marcucci, Clara D. Bloomfield, Ramiro Garzon

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2412-2415
Number of pages4
JournalBlood
Volume123
Issue number15
DOIs
StatePublished - Apr 10 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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