American Association for Cancer Research
21598290cd140104-sup-tab2.pdf (211.06 kB)

Supplementary Table S2 from Acquired Initiating Mutations in Early Hematopoietic Cells of CLL Patients

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journal contribution
posted on 2023-04-03, 21:20 authored by Frederik Damm, Elena Mylonas, Adrien Cosson, Kenichi Yoshida, Véronique Della Valle, Enguerran Mouly, M'boyba Diop, Laurianne Scourzic, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Yoshikane Kikushige, Frederick Davi, Jérôme Lambert, Daniel Gautheret, Hélène Merle-Béral, Laurent Sutton, Philippe Dessen, Eric Solary, Koichi Akashi, William Vainchenker, Thomas Mercher, Nathalie Droin, Seishi Ogawa, Florence Nguyen-Khac, Olivier A. Bernard

PDF file - 211KB, Biological and clinical features of the 24 patients included in the whole-exome study.



Appropriate cancer care requires a thorough understanding of the natural history of the disease, including the cell of origin, the pattern of clonal evolution, and the functional consequences of the mutations. Using deep sequencing of flow-sorted cell populations from patients with chronic lymphocytic leukemia (CLL), we established the presence of acquired mutations in multipotent hematopoietic progenitors. Mutations affected known lymphoid oncogenes, including BRAF, NOTCH1, and SF3B1. NFKBIE and EGR2 mutations were observed at unexpectedly high frequencies, 10.7% and 8.3% of 168 advanced-stage patients, respectively. EGR2 mutations were associated with a shorter time to treatment and poor overall survival. Analyses of BRAF and EGR2 mutations suggest that they result in deregulation of B-cell receptor (BCR) intracellular signaling. Our data propose disruption of hematopoietic and early B-cell differentiation through the deregulation of pre-BCR signaling as a phenotypic outcome of CLL mutations and show that CLL develops from a pre-leukemic phase.Significance: The origin and pathogenic mechanisms of CLL are not fully understood. The current work indicates that CLL develops from pre-leukemic multipotent hematopoietic progenitors carrying somatic mutations. It advocates for abnormalities in early B-cell differentiation as a phenotypic convergence of the diverse acquired mutations observed in CLL. Cancer Discov; 4(9); 1088–1101. ©2014 AACR.See related commentary by Jiang and Elemento, p. 995This article is highlighted in the In This Issue feature, p. 973

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