The genome of chemorefractory chronic lymphocytic leukemia reveals frequent mutations of NOTCH 1 and SF3B1

摘要

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults.1"3 The clinical course of CLL ranges from very indolent, with a nearly normal life expectancy,1 ~3 to rapidly progressive, leading to death, and occasionally undergoing transformation to aggressive lymphoma, known as Richter syndrome (RS).At presentation, several clinical and biological features may help predict, at least in part, the clinical course of CLL6"8 Of the biological prognosticators that have been developed, current guidelines for clinical practice recommend screening only for TP53 disruption by mutation and/or deletion of the locus, which identifies a fraction of high-risk CLL patients destined to experience a very short survival.8"15 High-risk CLL, however, cannot be fully recapitulated by TP53 disruption, as 40-50% high-risk CLL patients are devoid of TP53 abnormalities.16 Thus, it is conceivable that other genetic lesions may drive CLL aggressiveness and/or may cause the chemorefractory phenotype of the disease.