Clinical Risks for Chronic Lymphocytic Leukemia

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Jennifer R. Brown Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Harvard Medical School, Boston, MA

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Our understanding of risk factors for the development of chronic lymphocytic leukemia (CLL) is still incomplete and includes genetic and environmental factors. CLL is one of the most familial of all cancers, yet common high-penetrance risk alleles have not been identified. Genome-wide association studies have identified many common variants with low relative risks, whereas exome-wide rare variant analysis has implicated ATM in CLL causation. Environmental factors have also been challenging to identify given the limited understanding of the relevant time period of exposure relative to diagnosis, and the inability to quantify past exposures. Agent Orange and glyphosate herbicides have perhaps the most data to support their role. CLL is preceded by a precursor condition called monoclonal B-cell lymphocytosis (MBL), which could therefore be considered a risk factor, but which itself is likely caused by the same risk factors that ultimately give rise to CLL. Although virtually all people with CLL have a preceding MBL phase, most people with MBL will not develop CLL.

Submitted for publication December 15, 2023; accepted for publication February 20, 2024.

Disclosures: Dr. Brown has disclosed serving as a consultant for AbbVie, Acerta/AstraZeneca, Alloplex Biotherapeutics, BeiGene, Bristol Myers Squibb, Galapagos NV, Genentech/Roche, Grifols Worldwide Operations, InnoCare Pharma Inc, iOnctura, Kite, Loxo/Lilly, Merck, Numab Therapeutics, Pfizer, and Pharmacyclics; receiving grant/research support from BeiGene, Gilead Sciences, iOnctura, Loxo@Lilly, MEI Pharma, and TG Therapeutics; and serves as a scientific advisor for Grifols Therapeutics.

Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number R01 CA258924-01.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Correspondence: Jennifer R. Brown, MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215. Email: Jennifer_Brown@dfci.harvard.edu
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