Negative impact on clinical outcome of the mutational co-occurrence of SF3B1 and DNMT3A in refractory anemia with ring sideroblasts (RARS)

Data de publicació: 01/07/2017 Data Ahead of Print: 24/10/2016

Autors de IIS La Fe

Ivan Martin Castillo

Autor
Esperanza Such Taboada

Autor
María De La Encarnacion Lopez Pavia

Autor
Maria Amparo Ibañez Company

Autor
Eva Villamon Ribate

Autor
Inés Gómez Seguí

Autor
Irene Luna Del Valle

Autor
Juan Silvestre Oltra Soler

Autor
Laia Pedrola Vidal

Autor
Miguel Ángel Sanz Alonso

Autor
José Vicente Cervera Zamora

Autor
Guillermo Sanz Santillana

Autor

Autors aliens a IIS La Fe

Navarro, B
Vicente, A
Tormo, M

Grups d'Investigació

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos
Investigación Traslacional en Genética

Leader

Francisco Martínez Castellano

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 (SF3B1(mut)DNMT3A(mut)). 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 SF3B1(mut)DNMT3(Awt) patients. In conclusion, DNMT3A mutations are present in a significant proportion of SF3B1(mut) patients with a negative clinical impact.

Dades de la publicació

ISSN/ISSNe:: 1042-8194, 1029-2403
Tipus:: Article
Pàgines:: 1686-1693
DOI:: 10.1080/10428194.2016.1246725
PubMed:: 27771989
Factor d'Impacte:: 0,976 SCImago ℠
Quartil:: Q2 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Martin, I:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

b Department of Genomics , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain

Univ Hosp La Fe, Dept Genom, Valencia, Spain
Such, E:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain
Navarro, B:: c Department of Hematology , University Hospital Clinic , Valencia , Spain

Univ Hosp Clin, Dept Hematol, Valencia, Spain
Vicente, A:: d Department of Hematology , Hospital de la Ribera , Alzira, Spain

Hosp Ribera, Dept Hematol, Alzira, Spain
Lopez-Pavia, M:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, 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

Univ Hosp Clin, Dept Hematol, Valencia, Spain
Villamon, E:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain
Gomez-Segui, I:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain
Luna, I:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain
Oltra, S:: e Department of Genetics , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Genet, Valencia, Spain
Pedrola, L:: b Department of Genomics , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Genom, Valencia, Spain
Sanz, MA:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain
Cervera, J:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

e Department of Genetics , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain

Univ Hosp La Fe, Dept Genet, Valencia, Spain
Sanz, G:: a Department of Hematology , University Hospital La Fe , Valencia , Spain

Univ Hosp La Fe, Dept Hematol, Valencia, Spain

Keywords

SF3B1 mutations; ring sideroblasts; DNMT3A mutations; methyltransferase domain

Campos d'Estudi

Projectes associats

RED DE INVESTIGACION COOPERATIVA DE CANCER

RD06/0020/0031 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

CREACION Y MEJORA DE INFRAESTRUCTURAS EN MEDICINA REGENERATIVA

Investigador Principal: FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA

PLE2009-0141 ACI-PLAN E . MINISTERIO DE CIENCIA E INNOVACION; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009