title: 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.
authors.affiliation: Division of Hematology.
authors.forename: Violaine
authors.initials: V
authors.lastname: Havelange
authors.forename: Parvathi
authors.initials: P
authors.lastname: Ranganathan
authors.forename: Susan
authors.initials: S
authors.lastname: Geyer
authors.forename: Deedra
authors.initials: D
authors.lastname: Nicolet
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Huang
authors.forename: Xueyan
authors.initials: X
authors.lastname: Yu
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kornblau
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D000090243:Nucleophosmin