Research Papers:

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

Marta Cabezón, Joan Bargay, Blanca Xicoy, Olga García, Josep Borrás, Mar Tormo, Sílvia Marcé, Carme Pedro, David Valcárcel, Maria-José Jiménez, Ramón Guàrdia, Laura Palomo, Salut Brunet, Ferran Vall-Llovera, Antoni Garcia, Evarist Feliu and Lurdes Zamora On Behalf of the CETLAM Group _

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Oncotarget. 2018; 9:19342-19355. https://doi.org/10.18632/oncotarget.25046

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Marta Cabezón1,2, Joan Bargay3, Blanca Xicoy1, Olga García4, Josep Borrás3, Mar Tormo5, Sílvia Marcé1, Carme Pedro6, David Valcárcel7, Maria-José Jiménez1, Ramón Guàrdia8, Laura Palomo4, Salut Brunet9, Ferran Vall-Llovera10, Antoni Garcia11, Evarist Feliu1 and Lurdes Zamora1; On Behalf of the CETLAM Group

1Hematology Service, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain

2Departament de Medicina, Universitat Autònoma de Barcelona, Badalona, Spain

3Hematology Service, Hospital Son Llàtzer, Mallorca, Spain

4Josep Carreras Leukemia Research Institute, Campus Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain

5Hematology Service, Hospital Clínic de Valencia, Valencia, Spain

6Hematology Service, Hospital del Mar, Barcelona, Spain

7Hematology Service, Hospital Vall d’Hebron, Barcelona, Spain

8Hematology Service, ICO Girona-Hospital Josep Trueta, Girona, Spain

9Hematology Service, Hospital de Sant Pau, Barcelona, Spain

10Hematology Service, Hospital Mútua de Terrassa, Terrassa, Spain

11Hematology Service, Hospital Arnau de Vilanova, Lleida, Spain

Correspondence to:

Lurdes Zamora, email: [email protected]

Keywords: myelodysplastic syndromes; secondary acute myeloid leukemia; targeted deep sequencing; prognostic factors; 5-azacytidine

Received: December 06, 2017     Accepted: March 05, 2018     Published: April 10, 2018


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.

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