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EnglishNucleophosmin-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. © 2014 by The American Society of Hematology.
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| Data di pubblicazione: | 2014 | |
| Titolo: | Implications of the miR-10 family in chemotherapy response of NPM1-mutated AML | |
| Autori: | Havelange, Violaine; Ranganathan, Parvathi; Geyer, Susan; Nicolet, Deedra; Huang, Xiaomeng; Yu, Xueyan; Volinia, Stefano; Kornblau, Steven M.; Andreeff, Michael; Croce, Carlo M.; Marcucci, Guido; Bloomfield, Clara D.; Garzon, Ramiro | |
| Rivista: | BLOOD | |
| Parole Chiave: | Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Leukemia, Myeloid, Acute; Membrane Glycoproteins; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Receptors, Immunologic; Mutation; Hematology; Biochemistry; Cell Biology; Immunology | |
| Abstract in inglese: | 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. © 2014 by The American Society of Hematology. | |
| Digital Object Identifier (DOI): | 10.1182/blood-2013-10-532374 | |
| Handle: | http://hdl.handle.net/11392/2356336 | |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
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