American Association for Cancer Research
26433230bcd190058-sup-232231_2_supp_6719390_qjpcg1.pdf (16.51 kB)

Table S3 from Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy

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journal contribution
posted on 2023-04-04, 00:41 authored by Helene Kretzmer, Anat Biran, Noelia Purroy, Camilla K. Lemvigh, Kendell Clement, Michaela Gruber, Hongcang Gu, Laura Rassenti, Arman W. Mohammad, Connie Lesnick, Susan L. Slager, Esteban Braggio, Tait D. Shanafelt, Neil E. Kay, Stacey M. Fernandes, Jennifer R. Brown, Lili Wang, Shuqiang Li, Kenneth J. Livak, Donna S. Neuberg, Sven Klages, Bernd Timmermann, Thomas J. Kipps, Elias Campo, Andreas Gnirke, Catherine J. Wu, Alexander Meissner

Table of correlation between time points within one sample and number of hyper- or hypomethylated CpGs for all CLL (top) and naïve and memory B cell samples (bottom)



European Union


Instituto de Salud Carlos III, Madrid Spain

“La Caixa” Foundation

European Research Council

Institució Catalana de Recerca i Estudis Avançats




Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in preneoplastic monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significant differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and posttherapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state and a distinct expression profile together with MBL cells compared with normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically driven growth dynamics, and, together with its persistent presence, suggests a central role in disease onset. DNA methylation data from a large cohort of patients with MBL and CLL show that epigenetic transformation emerges early and persists throughout disease stages with limited subsequent changes. Our results indicate an early role for this aberrant landscape in the normal-to-preneoplastic transition that may reflect a pan-cancer mechanism.See related commentary by Rossi, p. 6.This article is highlighted in the In This Issue feature, p. 1

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