Affiliations 

  • 1 Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
  • 2 School of Health & Life Sciences, Teesside University, Middlesbrough TS1 3JN, UK
  • 3 Institute of Biosciences, International Centre for Life, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
  • 4 Department of Haematology, City Hospitals Sunderland NHS Trust, Sunderland SR4 7TP, UK
  • 5 Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK
Int J Mol Sci, 2020 Oct 16;21(20).
PMID: 33081245 DOI: 10.3390/ijms21207663

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. DRAK2 expression levels showed a positive correlation with the expression of DAPK1, and TGFBR1. Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-κB, and Akt and as critical signaling hubs upon DRAK2 knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.