Importance of genetics in chronic lymphocytic leukemia

Recurrent losses or gains of genomic material as well as mutations of key tumor suppressors (ATM and TP53) have been identified in chronic lymphocytic leukemia (CLL). These aberrations are important “drivers” of the disease and some of its clinical characteristics. There is a remarkable heterogeneity in the clinical course between patient subgroups with distinct genetic features. While some mutations are associated with poor outcome (particularly 17p− and TP53 mutation and to a lesser extend 11q−) others are linked to a favorable outcome (13q− as sole aberration; mutated IGHV). Our improved understanding of the clinical course of specific genetic subgroups is beginning to be translated into genotype specific treatment approaches where genetic subgroups (e.g. 17p−) are channeled into separate treatment protocols.This review will summarize the most important genetic aberrations in CLL and how our improved knowledge of the genetic make-up of leukemic cells may translate into improved treatment results.

Research Highlights
► Identification of new genetic lesions associated with refractory CLL.
► Identification of predictive factors aiding choice of therapy.
► Exploitation of specific vulnerabilities of genetic subgroups.