Negative impact on clinical outcome of the mutational co-occurrence ofSF3B1andDNMT3Ain refractory anemia with ring sideroblasts (RARS)
| Autor: | Irene Luna, Mariam Ibáñez, Mar Tormo, José Cervera, Blanca Navarro, Ivan Martin, Laia Pedrola, Esperanza Such, Eva Villamón, Silvestre Oltra, Ana Vicente, Guillermo Sanz, Inés Gómez-Seguí, Miguel A. Sanz, María López-Pavía |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Pathology Kaplan-Meier Estimate Ring sideroblasts Disease Biology Gastroenterology DNA Methyltransferase 3A 03 medical and health sciences 0302 clinical medicine Internal medicine Overall survival medicine Humans Genetic Predisposition to Disease In patient DNA (Cytosine-5-)-Methyltransferases Genetic Association Studies Aged Aged 80 and over Chromosome Aberrations Rbc transfusion Incidence (epidemiology) Anemia Refractory Myeloid leukemia Hematology Middle Aged Phosphoproteins Prognosis medicine.disease Anemia Sideroblastic Phenotype 030104 developmental biology Oncology 030220 oncology & carcinogenesis Refractory anemia with ring sideroblasts Mutation embryonic structures Female RNA Splicing Factors |
| Zdroj: | Leukemia & Lymphoma. 58:1686-1693 |
| ISSN: | 1029-2403 1042-8194 |
| DOI: | 10.1080/10428194.2016.1246725 |
| Popis: | The incidence of SF3B1 mutations in patients with RARS is high. Recently, it has been shown that SF3B1 and DNMT3A mutations overlap more often than expected, although it is not clear how this could affect the disease. We studied SF3B1 and DNMT3A in 123 RARS patients: 101 out of 123 samples (82%) had somatic mutations in SF3B1, and 13 of them (13%) showed a co-mutation (SF3B1mutDNMT3Amut). All co-mutated patients had a normal karyotype, and 12 of them (92%) were lower-risk patients (IPSS and IPSS-R). Despite their favorable profile, SF3B1mutDNMT3Amut patients showed a higher RBC transfusion dependency (92% versus 48%, p = .007), a shorter overall survival (OS) (median, 30 versus 97 months, p = .034), and a higher risk of progression to acute myeloid leukemia (AML) at 5 years (25% versus 2%, p = .023) than SF3B1mutDNMT3Awt patients. In conclusion, DNMT3A mutations are present in a significant proportion of SF3B1mut patients with a negative clinical impact. |
| Databáze: | OpenAIRE |
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