Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia

Abstract

Cytogenetic lesions do not completely explain clinical heterogeneity of chronic lymphocytic leukemia (CLL). The 2016 revision of the World Health Organization classification 2008 indicated that molecular lesions of TP53, NOTCH1, SF3B1 and BIRC3 have potential clinical relevance and could be integrated into an updated risk profile. The negative clinical implications of TP53 disruptions are well constituted and patients with these mutations should be considered for novel, small molecule signal transduction inhibitors therapies. Mutations of NOTCH1, SF3B1 and BIRC3 are associated with poor prognosis. Patients with mutated SF3B1 or NOTCH1 genes present shorter time to first treatment compared to unmutated group. NOTCH1 mutations are related to a high risk of Richter's syndrome transformation, especially in case of TP53 disruptions' coexistence. Large studies on MYD88 mutations in CLL have not explained clearly their clinical importance. The aim of this paper is to provide a comprehensive review on novel molecular aberrations identified in CLL.

Perspectives on Precision Medicine in Chronic Lymphocytic Leukemia: Targeting Recurrent Mutations—NOTCH1, SF3B1, MYD88, BIRC3

“…SF3B1 is a core component of the spliceosome, a complex of five small nuclear ribonucleoproteins RNA (snRNPs), the splicing machinery involved in the process of RNA editing through the removal of introns in protein-encoding genes [45]. The product of the SF3B1 gene is considered as an essential component that catalyses the removal of intronic sequences and ligates the exons into mature, functional mRNA [46].…”