New Study links Epigenetic Shifts toโค CLL Progression, Offeringโ Potential for Personalized โฃPrognosis
London, UK – Researchers have uncovered a strong correlation between fluctuating DNA โmethylation patterns and the clinical course of chronic lymphocytic leukemia (CLL), โa โcommon blood cancer. The findings, published today in Nature, suggest that tracking these epigenetic changes could refine risk assessment โand potentially guideโฃ treatment strategies for patients.The study analyzed data fromโฃ 231 CLL patients, tracking absolute lymphocyte counts over time – representingโฃ the number โof malignant cells โin the blood – and correlating these with โขevolutionary variables derived from a computational โคmodel called EVOFLUx. Researchers found that tumor growthโ rate โ(ฮธ), effective population size (Ne),โข and epigenetic switching rates were all โinformative of โขtime โto frist treatment (TTFT) and โoverallโ survival.
Specifically,theโ growth โคrate wasโ analyzed assuming exponential growth (where a ฮธ of 1โฃ equates to a 2.71-fold population increase per โขyear), Ne โwas considered per millionโฃ cells, and cancer age was โanalyzed in โ10-year increments. While individualโ epigenetic switching โrate parameters (ฮผ,ฮฝ,ฮณ,and ฮถ) proved largely uninformative on thier own,a combinedโ mean epigenetic switching rate – scaled by aโฃ factor of 100 – โshowed prognosticโค value.
Multivariate analysis incorporating growthโค rate, effective population size, TP53 aberrationsโ (mutations and deletions), IGHV gene mutational status, and patient age at โขsampling further โคrefined the predictive power of these evolutionary variables.Kaplan-Meierโ curves, generated using the maxstats package (v0.7-25) and โanalyzed with the log-rank โstatistic,demonstrated notable differences in โฃsurvival โขbased on low โversus high growth rates and effectiveโค population size withinโฃ IGHV subtypes.Notably,โ the study โcompared growth rates estimated by EVOFLUx with those derived from fitting linear models to past lymphocyte count data, validating the computational โapproach. all โขstatistical tests were two-sided, and appropriate โmultiple test โคcorrections, such as the Holm-Sidak correction, were applied โฃwhere โnecessary.The research utilized โขR (v4.3.1) with packages Survivalโ (v3.5-7), survminerโข (v0.4.9),โข ggsurvfitโ (v0.3.1), and โggplot2 (v3.5.2) forโฃ analysis โandโฃ visualization.