Skip to main content
Journal cover image

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

Publication ,  Journal Article
Brander, DM; Friedman, DR; Volkheimer, AD; Christensen, DJ; Rassenti, LZ; Kipps, TJ; Guadalupe, E; Chen, Y; Zhang, D; Wang, X; Davis, C ...
Published in: Br J Haematol
February 2019

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.

Duke Scholars

Published In

Br J Haematol

DOI

EISSN

1365-2141

Publication Date

February 2019

Volume

184

Issue

4

Start / End Page

605 / 615

Location

England

Related Subject Headings

  • Transcription Factors
  • Survival Rate
  • RNA, Neoplasm
  • RNA, Messenger
  • Protein Isoforms
  • Neoplasm Proteins
  • Middle Aged
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brander, D. M., Friedman, D. R., Volkheimer, A. D., Christensen, D. J., Rassenti, L. Z., Kipps, T. J., … Weinberg, J. B. (2019). SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia. Br J Haematol, 184(4), 605–615. https://doi.org/10.1111/bjh.15677
Brander, Danielle M., Daphne R. Friedman, Alicia D. Volkheimer, Dale J. Christensen, Laura Z. Rassenti, Thomas J. Kipps, Eross Guadalupe, et al. “SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia.Br J Haematol 184, no. 4 (February 2019): 605–15. https://doi.org/10.1111/bjh.15677.
Brander DM, Friedman DR, Volkheimer AD, Christensen DJ, Rassenti LZ, Kipps TJ, et al. SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia. Br J Haematol. 2019 Feb;184(4):605–15.
Brander, Danielle M., et al. “SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia.Br J Haematol, vol. 184, no. 4, Feb. 2019, pp. 605–15. Pubmed, doi:10.1111/bjh.15677.
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. SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia. Br J Haematol. 2019 Feb;184(4):605–615.
Journal cover image

Published In

Br J Haematol

DOI

EISSN

1365-2141

Publication Date

February 2019

Volume

184

Issue

4

Start / End Page

605 / 615

Location

England

Related Subject Headings

  • Transcription Factors
  • Survival Rate
  • RNA, Neoplasm
  • RNA, Messenger
  • Protein Isoforms
  • Neoplasm Proteins
  • Middle Aged
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology