Researchers say they have performed the first large-scale analysis of the chromatin landscape in chronic lymphocytic leukemia (CLL).
And, in doing so, they have identified shared gene regulatory networks as well as heterogeneity between patients and CLL subtypes.
The group says this work should enable deeper investigation into chromatin regulation in CLL and the identification of therapeutically relevant mechanisms of disease.
The work has been published in Nature Communications.
The researchers performed chromatin accessibility mapping—via the assay for transposase-accessible chromatin using sequencing (ATAC-seq)—on 88 CLL samples from 55 patients.
For 10 of the samples, the team also established histone profiles using ChIPmentation for 3 histone marks (H3K4me1, H3K27ac, and H3K27me3) and transcriptome profiles using RNA sequencing.
The researchers then developed a bioinformatic method for linking the chromatin profiles to clinical annotations and molecular diagnostics data, and they analyzed gene regulatory networks that underlie the major disease subtypes of CLL.
The work revealed a “shared core” of regulatory regions in CLL patients as well as variations between the samples.
Furthermore, the chromatin profiles and gene regulatory networks accurately predicted IGHV mutation status and pinpointed differences between IGVH-mutated and IGVH-unmutated CLL.
“Our study has been able to dissect the variability that exists in the epigenome of CLL patients and helped to identify disease-specific changes, which will hopefully be informative for distinguishing disease subtypes or identifying suitable treatments,” said study author Jonathan Strefford, PhD, of the University of Southampton in the UK.
“Epigenetics can offer a useful doorway into ways of improving disease diagnosis and more personalized treatment choices for patients.”
