CLL intraclonal fractions exhibit established and recently-acquired patterns of DNA methylation [GE]

Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Marked expression differences in intraclonal fractions suggest potential pathological and therapeutic relevance of studying intraclonal CLL fractions as compared to bulk cells. Genome-wide RNA expression profiling of sorted, fractionated peripheral blood mononuclear cell (PBMC) samples from patients with CLL. For 21 patients, enough data was obtained to study the both RNA expression and DNA methylation using Illumina 450K beadarrays in 4 fractions. Patients had known differences in IGHV mutational status , as well as cellular birth rates, as determined by labeling with deuterated water ingested by the patients.