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
Por:
Cabezón M., Bargay J., Xicoy B., García O., Borrás J., Tormo M., Marcé S., Pedro C., Valcárcel D., Jiménez M.-J., Guàrdia R., Palomo L., Brunet S., Vall-Llovera F., Garcia A., Feliu E., Zamora L.
Publicada:
10 abr 2018
Ahead of Print:
10 abr 2018
Resumen:
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 followup (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. © Cabezón et al.
Filiaciones:
Cabezón M.:
Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
Departament de Medicina, Universitat Autònoma de Barcelona, Badalona, Spain
Bargay J.:
Hematology Service, Hospital Son Llàtzer, Mallorca, Spain
Xicoy B.:
Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
García O.:
Josep Carreras Leukemia Research Institute, Campus Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
Borrás J.:
Hematology Service, Hospital Son Llàtzer, Mallorca, Spain
Tormo M.:
Hematology Service, Hospital Clínic de Valencia, Valencia, Spain
Marcé S.:
Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
Pedro C.:
Hematology Service, Hospital del Mar, Barcelona, Spain
Valcárcel D.:
Hematology Service, Hospital Vall d'Hebron, Barcelona, Spain
Jiménez M.-J.:
Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
Guàrdia R.:
Hematology Service, ICO Girona-Hospital Josep Trueta, Girona, Spain
Palomo L.:
Josep Carreras Leukemia Research Institute, Campus Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
Brunet S.:
Hematology Service, Hospital de Sant Pau, Barcelona, Spain
Vall-Llovera F.:
Hematology Service, Hospital Mútua de Terrassa, Terrassa, Spain
Garcia A.:
Hematology Service, Hospital Arnau de Vilanova, Lleida, Spain
Feliu E.:
Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
Zamora L.:
Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
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