Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A
| Autor: | James S. Blachly, Marius Bill, Clara D. Bloomfield, Christopher J. Walker, Bayard L. Powell, Krzysztof Mrózek, Albert de la Chapelle, Jonathan E. Kolitz, Andrew J. Carroll, Ann-Kathrin Eisfeld, Deedra Nicolet, Jessica Kohlschmidt, Shelley Orwick, Dimitrios Papaioannou, Richard Stone, John C. Byrd |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Neuroblastoma RAS viral oncogene homolog
Oncology Adult Male medicine.medical_specialty Adolescent Gene mutation medicine.disease_cause Translocation Genetic European LeukemiaNet Internal medicine medicine Humans Jacobsen Distal 11q Deletion Syndrome Aged Chromosome Aberrations Gene Rearrangement Multidisciplinary biology business.industry Myeloid leukemia Histone-Lysine N-Methyltransferase Biological Sciences Middle Aged medicine.disease PTPN11 Leukemia Leukemia Myeloid Acute KMT2A Treatment Outcome Karyotyping Mutation biology.protein Female KRAS business Myeloid-Lymphoid Leukemia Protein |
| Zdroj: | Proc Natl Acad Sci U S A |
| Popis: | Balanced rearrangements involving the KMT2A gene, located at 11q23, are among the most frequent chromosome aberrations in acute myeloid leukemia (AML). Because of numerous fusion partners, the mutational landscape and prognostic impact of specific 11q23/KMT2A rearrangements are not fully understood. We analyzed clinical features of 172 adults with AML and recurrent 11q23/KMT2A rearrangements, 141 of whom had outcome data available. We compared outcomes of these patients with outcomes of 1,097 patients without an 11q23/KMT2A rearrangement categorized according to the 2017 European LeukemiaNet (ELN) classification. Using targeted next-generation sequencing, we investigated the mutational status of 81 leukemia/cancer-associated genes in 96 patients with 11q23/KMT2A rearrangements with material for molecular studies available. Patients with 11q23/KMT2A rearrangements had a low number of additional gene mutations (median, 1; range 0 to 6), which involved the RAS pathway (KRAS, NRAS, and PTPN11) in 32% of patients. KRAS mutations occurred more often in patients with t(6;11)(q27;q23)/KMT2A-AFDN compared with patients with the other 11q23/KMT2A subsets. Specific gene mutations were too infrequent in patients with specific 11q23/KMT2A rearrangements to assess their associations with outcomes. We demonstrate that younger (age |
| Databáze: | OpenAIRE |
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