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Series GSE125499 Query DataSets for GSE125499
Status Public on Feb 23, 2021
Title The altered DNA methylation landscape in chronic lymphocytic leukemia emerges early and persists after treatment
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary 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<<<
Contributor(s) Kretzmer H, Clement K, Gruber M, Gu H, Anat B, Rassenti L, Purroy N, Lesnick C, Kay NE, Arman M, Wang L, Neuberg D, Timmermann B, Campo E, Kipps T, Gnirke A, Wu C, Meissner A
Citation(s) 33604581
Submission date Jan 23, 2019
Last update date Feb 23, 2021
Contact name Helene Kretzmer
Organization name Max Planck Institute for Molecular Genetics
Department Genome Regulation
Lab Meissner Lab
Street address Ihnestraße 63
City Berlin
ZIP/Postal code 14195
Country Germany
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (368)
GSM3575651 1A
GSM3575652 1B
GSM3575653 1C
BioProject PRJNA516635

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Supplementary file Size Download File type/resource
GSE125499_RAW.tar 5.5 Gb (http)(custom) TAR (of BW)
Processed data provided as supplementary file
Raw data not provided for this record

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