TY - JOUR
T1 - DNA methylation profile in chronic myelomonocytic leukemia associates with distinct clinical, biological and genetic features
AU - Palomo, Laura
AU - Malinverni, Roberto
AU - Cabezón, Marta
AU - Xicoy, Blanca
AU - Arnan, Montserrat
AU - Coll, Rosa
AU - Pomares, Helena
AU - García, Olga
AU - Fuster-Tormo, Francisco
AU - Grau, Javier
AU - Feliu, Evarist
AU - Solé, Francesc
AU - Buschbeck, Marcus
AU - Zamora, Lurdes
PY - 2018/1/2
Y1 - 2018/1/2
N2 - © 2018 Informa UK Limited, trading as Taylor & Francis Group. 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.
AB - © 2018 Informa UK Limited, trading as Taylor & Francis Group. 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.
KW - Chronic myelomonocytic leukemia
KW - DNA methylation
KW - TET2
KW - hypermethylation
KW - prognosis
U2 - 10.1080/15592294.2017.1405199
DO - 10.1080/15592294.2017.1405199
M3 - Article
C2 - 29160764
VL - 13
SP - 8
EP - 18
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 1
ER -