The inherited genetic contribution and polygenic risk score for risk of CLL and MBL: a narrative review

Abstract

Chronic lymphocytic leukemia (CLL) is a neoplasm of B-cells in the blood and monoclonal B-cell lymphocytosis (MBL) is a precursor state to CLL. This narrative review provides an overview of the genetic studies that identified 43 common variants associated with risk of CLL among individuals of European ancestry. Emerging studies found that ∼50% of these variants are associated with MBL risk. Moreover, the polygenic risk score (PRS) calculated from these CLL variants has been shown to be a robust predictor for both CLL and MBL risk among European ancestry individuals but a weak predictor among African ancestry individuals. By summarizing these genetic studies, we conclude that additional studies are needed in other race/ethnic populations to identify race-specific susceptibility variants, that functional studies are needed to validate the biological mechanisms of the variants, and that the clinical utility of the PRS is limited until preventive strategies for CLL are developed.

Keywords:

• CLL
• PRS
• MBL

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Institutes of Health (NIH) [grants R01 AG58266, R01 CA235026, R01 CA254951, and R21 CA256648], and also supported by National Cancer Institute and National Institute on Aging.