DNA methylation profile in chronic myelomonocytic leukemia associates with distinct clinical,biological and genetic features |
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| Authors: | Laura Palomo Roberto Malinverni Marta Cabezón Blanca Xicoy Montserrat Arnan Rosa Coll |
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| Institution: | 1. MDS Group. Josep Carreras Leukaemia Research Institute (IJC), ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera de Can Ruti, Camí de les Escoles, s/n. 08916, Badalona (Barcelona), Spain;2. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Campus de la UAB, Pla?a Cívica, s/n. 08913, Bellaterra (Barcelona), Spain;3. Chromatin, Metabolism and Cell Fate Group. Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Hospital Germans Trias i Pujol, Program for Predictive and Personalized Medicine of Cancer at the Institute Germans Trias i Pujol (PMPPC-IGTP), Carretera de Can Ruti, Camí de les Escoles, s/n. 08916, Badalona (Barcelona), Spain;4. Hematology Service, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute (IJC), Universitat Autònoma de Barcelona, Carretera del Canyet, s/n. 08916, Badalona (Barcelona), Spain;5. Hematology Service, ICO-Hospital Duran i Reynals, Avinguda de la Gran Via de l'Hospitalet, 199–203, 08908 Hospitalet de Llobregat (Barcelona), Spain;6. Hematology Service, ICO-Girona Hospital Josep Trueta, Girona, Spain, Avenida Fran?a, s/n. 17007 Girona, Spain |
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| Abstract: | Chromosomal abnormalities are detected in 20–30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation, including hypermethylation of specific genes and large genome regions with aberrant DNA methylation. Unsupervised hierarchical cluster analysis identified two main clusters that associated with the clinical, biological, and genetic features of patients. Group 1 was enriched in patients with adverse clinical and biological characteristics and poorer overall and progression-free survival. In addition, significant differences in DNA methylation were observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild type patients. Taken together, our results demonstrate that altered DNA methylation patterns reflect the CMML disease state and allow to identify patient groups with distinct clinical features. |
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| Keywords: | Chronic myelomonocytic leukemia DNA methylation hypermethylation prognosis TET2 |
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