Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors
| Autor: | Guy Sauvageau, Josée Hébert, Caroline Pabst, Cynthia J. Guidos, Sébastien Lemieux, Isabel Boivin, Geneviève Boucher, Jana Krosl, Vincent-Philippe Lavallée, Sylvain Meloche, Patrick Gendron, Anne Marinier |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent DNA Mutational Analysis Immunology Disease Biology medicine.disease_cause Biochemistry Cohort Studies Young Adult 03 medical and health sciences Gene Frequency Receptors Colony-Stimulating Factor CEBPA Tumor Cells Cultured medicine Humans Precision Medicine Receptor Protein Kinase Inhibitors Gene Sensitization Aged Janus Kinases Aged 80 and over Genetics Mutation Gene Expression Profiling High-Throughput Nucleotide Sequencing Myeloid leukemia Cell Biology Hematology Middle Aged medicine.disease Leukemia Myeloid Acute Leukemia 030104 developmental biology medicine.anatomical_structure Drug Resistance Neoplasm CCAAT-Enhancer-Binding Proteins Cancer research Female Drug Screening Assays Antitumor Transcriptome |
| Zdroj: | Blood. 127:3054-3061 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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