Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178606
Title: Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features
Author: Palomo, Laura
Garcia, Olga
Arnan, Montserrat
Xicoy Cirici, Blanca
Fuster, Francisco
Cabezón, Marta
Coll, Rosa
Ademà, Vera
Grau, Javier
Jimenez, Maria Jose
Pomares, Helena
Marcé Roca, Silvia
Mallo, Mar
Millá, Fuensanta
Alonso Sanz, Esther
Sureda, Anna
Gallardo, David
Feliu, Evarist
Ribera, Josep Maria
Solé Ristol, Francesc
Zamora, Lurdes
Keywords: Seqüència de nucleòtids
Leucèmia
Genètica
Nucleotide sequence
Leukemia
Genetics
Issue Date: 30-Aug-2016
Publisher: Impact Journals
Abstract: Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC.
Note: Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.10937
It is part of: Oncotarget, 2016, vol. 7, num. 35, p. 57021-57035
URI: http://hdl.handle.net/2445/178606
Related resource: https://doi.org/10.18632/oncotarget.10937
ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)

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