Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib
| Autor: | Madan G. Luthra, Srdan Verstovsek, Mark J. Routbort, Elias Jabbour, Rajesh R. Singh, Meenakshi Mehrotra, Kate J. Newberry, Hagop M. Kantarjian, Rajyalakshmi Luthra, Jorge E. Cortes, Fabio P.S. Santos, Taghi Manshouri, Sherry Pierce, Keyur P. Patel |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Neuroblastoma RAS viral oncogene homolog Oncology Ruxolitinib medicine.disease_cause Biochemistry Odds Ratio Medicine Aged 80 and over Myeloid Neoplasia High-Throughput Nucleotide Sequencing Hematology Middle Aged Prognosis Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic Female KRAS Receptors Thrombopoietin medicine.drug Adult medicine.medical_specialty Immunology Antineoplastic Agents Dioxygenases Proto-Oncogene Proteins Internal medicine Nitriles Humans Myelofibrosis Protein Kinase Inhibitors Survival analysis Aged business.industry Gene Expression Profiling Cell Biology Odds ratio Janus Kinase 2 medicine.disease Survival Analysis Discontinuation Repressor Proteins PTPN11 Pyrimidines Primary Myelofibrosis Mutation Pyrazoles Calreticulin business Spleen |
| Zdroj: | Blood. 126:790-797 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2015-03-633404 |
| Popis: | Although most patients with myelofibrosis (MF) derive benefit from ruxolitinib, some are refractory, have a suboptimal response, or quickly lose their response. To identify genes that may predict response to ruxolitinib, we performed targeted next-generation sequencing (NGS) of a panel of 28 genes recurrently mutated in hematologic malignancies in a cohort of patients with MF who were treated with ruxolitinib in a phase 1/2 study. We also tested for CALR deletions by standard polymerase chain reaction methods. Ninety-eight percent of patients had a mutation in ≥1 gene. Seventy-nine (82.1%) patients had the JAK2(V617F) mutation, 9 (9.5%) had CALR mutations (7 type 1, 2 type 2), 3 (3.1%) had MPL mutations, and 4 (4.2%) were negative for all 3. ASXL1/JAK2 and TET2/JAK2 were the most frequently comutated genes. Mutations in NRAS, KRAS, PTPN11, GATA2, TP53, and RUNX1 were found in |
| Databáze: | OpenAIRE |
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