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

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.

journal_name

Blood

journal_title

Blood

authors

Havelange V,Ranganathan P,Geyer S,Nicolet D,Huang X,Yu X,Volinia S,Kornblau SM,Andreeff M,Croce CM,Marcucci G,Bloomfield CD,Garzon R

doi

10.1182/blood-2013-10-532374

subject

Has Abstract

pub_date

2014-04-10 00:00:00

pages

2412-5

issue

15

eissn

0006-4971

issn

1528-0020

pii

blood-2013-10-532374

journal_volume

123

pub_type

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