SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia.

Published

Journal Article

Alteration in RNA splicing is implicated in carcinogenesis and progression. Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (CLL), a common B cell malignancy with heterogeneous outcomes. We previously demonstrated that differences in the amount of SET oncoprotein (a physiological inhibitor of the serine/threonine phosphatase, PP2A) is associated with clinical aggressiveness in patients with CLL. It is unknown if alternative splicing of gene transcripts regulating kinases and phosphatases affects disease pathobiology and CLL progression. We show here for the first time that mRNA levels of the alternatively spliced SET isoforms, SETA and SETB (SETα and SETβ), significantly correlate with disease severity (overall survival and time-to-first-treatment) in CLL patients. In addition, we demonstrate that relative increase of SETA to SETB mRNA can discriminate patients with a more aggressive disease course within the otherwise favourable CLL risk classifications of IGHV mutated and favourable hierarchical fluorescence in situ hybridisation groups. We validate our finding by showing comparable relationships of SET mRNA with disease outcomes using samples from an independent CLL cohort from a separate institution. These findings indicate that alternative splicing of SET, and potentially other signalling cascade molecules, influences CLL biology and patient outcomes.

Full Text

Duke Authors

Cited Authors

  • Brander, DM; Friedman, DR; Volkheimer, AD; Christensen, DJ; Rassenti, LZ; Kipps, TJ; Guadalupe, E; Chen, Y; Zhang, D; Wang, X; Davis, C; Owzar, K; Weinberg, JB

Published Date

  • February 2019

Published In

Volume / Issue

  • 184 / 4

Start / End Page

  • 605 - 615

PubMed ID

  • 30443898

Pubmed Central ID

  • 30443898

Electronic International Standard Serial Number (EISSN)

  • 1365-2141

International Standard Serial Number (ISSN)

  • 0007-1048

Digital Object Identifier (DOI)

  • 10.1111/bjh.15677

Language

  • eng