期刊
BLOOD
卷 127, 期 24, 页码 3054-3061出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2016-03-705053
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资金
- Government of Canada through Genome Canada
- Ministere de l'economie, de l'innovation et des exportations du Quebec through Genome Quebec
- AmorChem
- Canadian Cancer Society Research Institute
- research chairs from the Canada Research Chair program
- Industrielle-Alliance (Universite de Montreal)
- Cancer Research Network of the Fonds de recherche du Quebec-Sante
- Canada Foundation for Innovation
- NanoQuebec
- Reseau de medecine genetique appliquee
- Fonds de recherche du Quebec-Nature et technologies
- Cole Foundation
- German Cancer Aid
In this study, we analyzed RNA-sequencing data of 14 samples characterized by biallelic CEBPA (CEBPA(bi)) mutations included in the Leucegene collection of 415 primary acute myeloid leukemia (AML) specimens, and describe for the first time high frequency recurrent mutations in the granulocyte colony-stimulating factor receptor gene CSF3R, which signals through JAK-STAT proteins. Chemical interrogation of these primary human specimens revealed a uniform and specific sensitivity to all JAK inhibitors tested irrespective of their CSF3R mutation status, indicating a general sensitization of JAK-STAT signaling in this leukemia subset. Altogether, these results identified the co-occurrence of mutations in CSF3R and CEBPA in a well-defined AML subset, which uniformly responds to JAK inhibitors and paves the way to personalized clinical trials for this disease.
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