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Dynamics of DNA Methylation in CLL Patients Treated With Chemoimmunotherapy

By: Anna Nowogrodzki
Posted: Monday, February 10, 2020

DNA methylation patterns change after relapse in some patients with chronic lymphocytic leukemia (CLL), particularly those who take longer to relapse, according to a new study published in Clinical Epigenetics. Kostas Stamatopoulos, MD, PhD, of the Institute of Applied Biosciences at the Center for Research and Technology Hellas in Thessaloniki, Greece, and colleagues noted that these epigenetic alterations appear to be linked to specific clinical and biologic features.

“DNA methylation profiles are modulated during chronic lymphocytic leukemia evolution,” the authors wrote, “in response to chemoimmunotherapy with the fludarabine-cyclophosphamide-rituximab regimen.”

The authors performed DNA methylation analysis on samples from 34 patients with CLL treated with chemoimmunotherapy. A total of 31 patients were treated with the fludarabine-cyclophosphamide-rituximab regimen, and most (29) had the U-CLL subset—which is associated with an adverse prognosis and a higher incidence of progression of disease requiring treatment, according to the authors. The researchers analyzed a pretreatment sample and a postrelapse sample from each patient. The median time between these two samples was 2.5 years, with a range of 0.75 to 10.9 years. The authors also compared pretreatment samples with memory B cells from healthy donors.

CLL cells had much more highly methylated DNA than memory B cells from healthy controls. DNA methylation profiles were too variable to see changes at a cohort level, they noted. At an individual level, a higher epigenetic burden (the number of methylation changes compared with healthy memory B cells) was associated with a shorter time to first treatment.

Comparing each patient’s methylation between the pretreatment and postrelapse samples, the authors found that some changed very little, whereas others showed either significantly more or significantly less DNA methylation after relapse. Patients who relapsed sooner, especially within 2 years of treatment, tended to be less likely to show changes in their DNA methylation patterns.

Disclosure: For full disclosures of the study authors, visit clinicalepigeneticsjournal.biomedcentral.com.



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