TY - JOUR
T1 - Implications of the miR-10 family in chemotherapy response of NPM1-mutated AML
AU - Havelange, Violaine
AU - Ranganathan, Parvathi
AU - Geyer, Susan
AU - Nicolet, Deedra
AU - Huang, Xiaomeng
AU - Yu, Xueyan
AU - Volinia, Stefano
AU - Kornblau, Steven M.
AU - Andreeff, Michael
AU - Croce, Carlo M.
AU - Marcucci, Guido
AU - Bloomfield, Clara D.
AU - Garzon, Ramiro
PY - 2014/4/10
Y1 - 2014/4/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84901717408&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901717408&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-10-532374
DO - 10.1182/blood-2013-10-532374
M3 - Article
C2 - 24596420
AN - SCOPUS:84901717408
SN - 0006-4971
VL - 123
SP - 2412
EP - 2415
JO - Blood
JF - Blood
IS - 15
ER -