Methylation markers identify high risk patients in IGHV mutated chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) exhibits a very variable clinical course. Altered DNA methylation of genes has shown promise as a source of novel prognostic makers in a number of cancers. Here we have studied the potential utility of a panel of methylation markers (CD38, HOXA4 and BTG4) in 118 CLL patients. Each of the three loci assessed exhibited frequent methylation, as determined by COBRA analysis, and individually correlated with either good (CD38, BTG4 methylation) or poor (HOXA4 methylation) prognosis. Using a combined approach to produce an overall methylation score, we found that methylation score was significantly associated with time to first treatment in CLL patients. Multivariate Cox regression analysis revealed that methylation score was the strongest predictor of time to first treatment, and was independent of IGHV gene mutational status and CD38 expression. This study provides proof of principle that a panel of methylation markers can be used for additional risk stratification of CLL patients.
Crucible Laboratory, Institute for Ageing and Health, Newcastle University, UK.
Laura
L
Irving
Tryfonia
T
Mainou-Fowler
Anton
A
Parker
Rachel E
RE
Ibbotson
David G
DG
Oscier
Gordon
G
Strathdee
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016016:Proportional Hazards Models; D012307:Risk Factors; D014157:Transcription Factors
C415579:BTG4 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D014157:Transcription Factors; C073547:HOXA4 protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1