title: Negative impact on clinical outcome of the mutational co-occurrence of SF3B1 and DNMT3A in refractory anemia with ring sideroblasts (RARS).
abstract: 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, SF3B1mutDNMT3Amutpatients 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 SF3B1mutDNMT3Awtpatients. In conclusion, DNMT3A mutations are present in a significant proportion of SF3B1mutpatients with a negative clinical impact.
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.|b Department of Genomics , University Hospital La Fe , Valencia , Spain.
authors: Iván
authors: I
authors: Martín
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Esperanza
authors: E
authors: Such
authors: c Department of Hematology , University Hospital Clinic , Valencia , Spain.
authors: Blanca
authors: B
authors: Navarro
authors: d Department of Hematology , Hospital de la Ribera , Alzira, Spain.
authors: Ana
authors: A
authors: Vicente
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: María
authors: M
authors: López-Pavía
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Mariam
authors: M
authors: Ibáñez
authors: c Department of Hematology , University Hospital Clinic , Valencia , Spain.
authors: Mar
authors: M
authors: Tormo
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Eva
authors: E
authors: Villamón
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Inés
authors: I
authors: Gómez-Seguí
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Irene
authors: I
authors: Luna
authors: e Department of Genetics , University Hospital La Fe , Valencia , Spain.
authors: Silvestre
authors: S
authors: Oltra
authors: b Department of Genomics , University Hospital La Fe , Valencia , Spain.
authors: Laia
authors: L
authors: Pedrola
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Miguel Angel
authors: MA
authors: Sanz
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.|e Department of Genetics , University Hospital La Fe , Valencia , Spain.
authors: Jose
authors: J
authors: Cervera
authors: a Department of Hematology , University Hospital La Fe , Valencia , Spain.
authors: Guillermo
authors: G
authors: Sanz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D000756:Anemia, Sideroblastic / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D002869:Chromosome Aberrations; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D011379:Prognosis; D000072260:RNA Splicing Factors / Q000235:genetics*
chemical_list: C000717967:DNMT3A protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; C112491:SF3B1 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: DNMT3A mutations; SF3B1 mutations; methyltransferase domain; ring sideroblasts