Journal
ONCOTARGET
Volume 7, Issue 35, Pages 57021-57035Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10937
Keywords
chronic myelomonocytic leukemia; normal karyotype; gene mutations; targeted deep sequencing; prognostic factors
Categories
Funding
- Ministerio de Educacion Cultura y Deporte [FPU13/03770]
- Instituto de Salud Carlos III, Ministerio de Economia y Competividad, Spain [PI 11/02519, PI 11/02010, PI 14/00013]
- Red Tematica de Investigacion Cooperativa en Cancer (RTICC, FEDER) [RD12/0036/0044]
- Generalitat de Catalunya [2014 SGR225 (GRE)]
- Fundacio Internacional Josep Carreras, Obra Social la Caixa and Celgene Spain
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available