Web of Science: 22 citations, Scopus: 23 citations, Google Scholar: citations,
Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features
Palomo Sanchis, Laura (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
García, Olga (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Arnan, Montse (Institut Català d'Oncologia)
Xicoy, Blanca (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Fuster García, Francisco (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cabezón, Marta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Coll, Rosa (Hospital Universitari de Girona Doctor Josep Trueta)
Ademà Llobet, Vera (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Grau Cat, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Jiménez, Maria-José (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Pomares, Helena (Institut Català d'Oncologia)
Marcé, Sílvia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Mallo, Mar (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Millá, Fuensanta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Alonso, Esther (Institut Català d'Oncologia)
Sureda, Anna (Institut Català d'Oncologia)
Gallardo, David (Hospital Universitari de Girona Doctor Josep Trueta)
Feliu Frasnedo, Evarist (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Solé, Francesc (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Zamora, Lurdes (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date: 2016
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 (TET2 wt) 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.
Grants: Ministerio de Educación, Cultura y Deporte FPU2013-03770
Ministerio de Economía y Competitividad PI/11-02519
Ministerio de Economía y Competitividad PI/11-02010
Ministerio de Economía y Competitividad PI/14-00013
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-225
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. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Chronic myelomonocytic leukemia ; Normal karyotype ; Gene mutations ; Targeted deep sequencing ; Prognostic factors
Published in: Oncotarget, Vol. 7, Num. 35 (August 2016) , p. 57021-57035, ISSN 1949-2553

DOI: 10.18632/oncotarget.10937
PMID: 27486981


15 p, 2.2 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
Articles > Research articles
Articles > Published articles

 Record created 2018-02-07, last modified 2022-04-27



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