BioProject

Here we measured genome-wide DNA methylation in patients with chronic lymphocytic leukemia as it provides an opportunity to capture the emergence of altered methylation landscapes as well as track their dynamics over disease progression including after treatment. Specifically, our cohort includes 21 CLL cases with up to six different time points, 20 precursor states of monoclonal B cell lymphocytes (MBL) and 5 matched samples from MBL and CLL states of the same patients. We find that across all CLL cases, a highly aberrant methylation state was present consistently already at the first time point and maintained with remarkable stability over disease progression. To improve our resolution and address heterogeneity we sequenced the methylome of single cells from CD5 positive and negative naïve and memory B cells as well as unsorted B cells and CLL cells. Methylation levels were highly similar within groups pointing to a rather homogeneous population and contrasted by pronounced differences between naïve and memory B cells that do not distinguish CD5 positive and negative subgroups. Our 20 patients with MBL further confirmed the early emergence of this landscape and surprisingly, the chemotherapy did not have a notable impact on the altered methylome despite a strong depletion of white blood cells. Overall design: RRBS and scRRBS data was collected on CLL and MBL diagnosed individuals. Each CLL patient was sequenced at two to six time points and white blood counts were tracked. Single cell RRBS was performed in 96-well plates for 48 cells of CLL cells from two individuals. Samples include unsorted B cells as well as CD5 positive and negative naive and memory B cells from two healthy individuals. >>>Submitter states that raw data will be submitted to dbGaP<<<