Time to relapse in chronic lymphocytic leukemia and DNA-methylation-based biological age

Abstract

Chronic lymphocytic leukemia (CLL) is a mature B cell neoplasm with a predilection for older individuals. While previous studies have identified epigenetic signatures associated with CLL, whether age-related DNA methylation changes modulate CLL relapse remains elusive. In this study, we examined the association between epigenetic age acceleration and time to CLL relapse in a publicly available dataset. DNA methylation profiling of 35 CLL patients prior to initiating chemoimmunotherapy was performed using the Infinium HumanMethylation450 BeadChip. Four epigenetic age acceleration metrics (intrinsic epigenetic age acceleration [IEAA], extrinsic epigenetic age acceleration [EEAA], PhenoAge acceleration [PhenoAA], and GrimAge acceleration [GrimAA]) were estimated from blood DNA methylation levels. Linear, quantile, and logistic regression and receiver operating characteristic curve analyses were conducted to assess the association between each epigenetic age metric and time to CLL relapse. EEAA (p = 0.011) and PhenoAA (p = 0.046) were negatively and GrimAA (p = 0.040) was positively associated with time to CLL relapse. Simultaneous assessment of EEAA and GrimAA in male patients distinguished patients who relapsed early from patients who relapsed later (p = 0.039). No associations were observed with IEAA. These findings suggest epigenetic age acceleration prior to chemoimmunotherapy initiation is associated with time to CLL relapse. Our results provide novel insight into the association between age-related DNA methylation changes and CLL relapse and may serve has biomarkers for treatment relapse, and potentially, treatment selection.

Aging and Age-Related Epigenetic Drift in the Pathogenesis of Leukemia and Lymphomas: New Therapeutic Targets

“…With IEAA, no relationships were found. These results imply that the time to CLL relapse is correlated with epigenetic age acceleration prior to the start of chemotherapy [132]. These findings offer fresh understanding of the relationship between aging-related DNA methylation alterations and CLL recurrence, and could potentially serve as indicators for treatment relapse and therapy choice.…”

“…In a publicly available dataset, a study [132] investigated the relationship between epigenetic age acceleration and time to CLL relapse. Before starting chemoimmunotherapy, the Infinium HumanMethylation450 BeadChip was used to analyze the DNA methylation of 35 CLL patients.…”

Genetically Determined Telomere Length and Risk for Haematologic Diseases: Results from Large Prospective Cohorts and Mendelian Randomization Analysis

“…Speci cally, they found that the Hannum age acceleration and PhenoAge acceleration were inversely related to the time of CLL relapse, whereas the GrimAge acceleration was positively associated with relapse duration. 54 The underlying mechanisms of the causative role of telomere length and EAA in haematological malignancies may be quite complex. Our study ndings suggest that longer telomeres are linked to a higher risk of most haematologic malignancies, but they do not signi cantly in uence the risk of benign haematologic diseases.…”

Biological age is superior to chronological age in predicting hospital mortality of the critically ill

“…First, clinicians have long held an intuition that biological or phenotypical age is more important than chronological age in determining health outcomes, and chronological age is an imperfect marker of one’s physiological reserve or ‘effective age’ [ 10 , 12 ]. With intensive computing capability including the use of artificial intelligence, a few phenotypical or biological age estimation models that are predictive of long-term functional and survival outcomes in a wide range of clinical settings have been developed [ 7 – 10 , 13 – 16 ]. The utility of biological age in acute care setting has, however, not been thoroughly assessed.…”