SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia

CLL is a heterogeneous disease with a variable clinical course and response to therapy. New genetic lesions have been noted in subgroups of patients through whole-exome and whole-genome sequencing. An abnormality in RNA splicing has been found in 15% of patients. Chronic lymphocytic leukemia is an incurable disease characterized by extensive clinical heterogeneity despite a common diagnostic immunophenotype (surface expression of CD19+, CD20+dim, CD5+, CD23+, and sIgMdim). Whereas the course of disease is indolent in some patients, it is steadily progressive in approximately half of patients, leading to substantial morbidity and mortality. 1 Our ability to predict a more aggressive disease course has improved with the use of tests for biologic markers (degree of somatic hypermutation in the variable region of the immunoglobulin heavy chain [ IGHV ] gene and expression of ZAP70) and the detection of cytogenetic abnormalities (deletions . . .