Negative impact on clinical outcome of the mutational co-occurrence of SF3B1 and DNMT3A in refractory anemia with ring sideroblasts (RARS)
Por:
Martín I, Such E, Navarro B, Vicente A, López-Pavía M, Ibáñez M, Tormo M, Villamón E, Gómez-Seguí I, Luna I, Oltra S, Pedrola L, Sanz MA, Cervera J and Sanz G
Publicada:
1 ene 2017
Ahead of Print:
24 oct 2016
Resumen:
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. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Filiaciones:
Martín I:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
b Department of Genomics , University Hospital La Fe , Valencia , Spain
Such E:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Navarro B:
c Department of Hematology , University Hospital Clinic , Valencia , Spain
:
d Department of Hematology , Hospital de la Ribera , Alzira, Spain
López-Pavía M:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Ibáñez M:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Tormo M:
c Department of Hematology , University Hospital Clinic , Valencia , Spain
Villamón E:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Gómez-Seguí I:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Luna I:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Oltra S:
e Department of Genetics , University Hospital La Fe , Valencia , Spain
Pedrola L:
b Department of Genomics , University Hospital La Fe , Valencia , Spain
Sanz MA:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
Cervera J:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
e Department of Genetics , University Hospital La Fe , Valencia , Spain
Sanz G:
a Department of Hematology , University Hospital La Fe , Valencia , Spain
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