Impact of mutational studies on the diagnosis and the outcome of high-risk myelodysplastic syndromes and secondary acute myeloid leukemia patients treated with 5-azacytidine
Cabezón, Marta (Universitat Autònoma de Barcelona. Departament de Medicina)
Bargay, Joan (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears))
Xicoy, Blanca (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
García, Olga (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Borrás, Josep (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears))
Tormo, Mar (Hospital Clínic Universitari (València))
Marcé, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pedro, Carme (Hospital del Mar (Barcelona, Catalunya))
Valcárcel, David (Hospital Universitari Vall d'Hebron)
Jiménez, Maria José (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Guàrdia, Ramón (Hospital Universitari de Girona Doctor Josep Trueta)
Palomo Sanchís, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Brunet, Salut (Institut d'Investigació Biomèdica Sant Pau)
Vall-Llovera, Ferran (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Garcia, Antoni (Hospital Arnau de Vilanova (Lleida, Catalunya))
Feliu Frasnedo, Evarist (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Zamora, Lurdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Myelodysplastic syndromes (MDS) are stem cell disorders caused by various gene abnormalities. We performed targeted deep sequencing in 39 patients with high-risk MDS and secondary acute myeloid leukemia (sAML) at diagnosis and follow-up (response and/or relapse), with the aim to define their mutational status, to establish if specific mutations are biomarkers of response to 5-azacytidine (AZA) and/or may have impact on survival. Overall, 95% of patients harbored at least one mutation. TP53, DNMT3A and SRSF2 were the most frequently altered genes. Mutations in TP53 correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS) in univariate analysis. Patients with SRSF2 mutations were associated with better OS and PFS. Response rate was 55%; but we could not correlate the presence of TET2 and TP53 mutations with AZA response. Patients with sAML presented more variations than patients with high-risk MDS, and usually at relapse the number of mutations increased, supporting the idea that in advanced stages of the disease there is a greater genomic complexity. These results confirm that mutation analysis can add prognostic value to high-risk MDS and sAML patients, not only at diagnosis but also at follow-up.
Grants:	Instituto de Salud Carlos III PI/11/02519 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014 SGR225
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Myelodysplastic syndromes ; Secondary acute myeloid leukemia ; Targeted deep sequencing ; Prognostic factors ; 5-azacytidine
Published in:	Oncotarget, Vol. 9 (april 2018) , p. 19342-19355, ISSN 1949-2553

DOI: 10.18632/oncotarget.25046
PMID: 29721207

14 p, 1.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles