DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia

Research output: Contribution to journalArticle

DOI

Authors

  • Katarzyna Szoltysek
  • Carmela Ciardullo
  • Peixun Zhou
  • Anna Walaszczyk
  • Elaine Willmore
  • Vikki Rand
  • Scott Marshall
  • Andy Hall
  • Christine J. Harrison
  • Jeyanthy Eswaran
  • Meera Soundararajan

Departments

External departments

  • Newcastle University
  • Maria Sklodowska-Curie Institute of Oncology
  • Teesside University
  • City Hospitals Sunderland NHS Foundation Trust

Details

Original languageEnglish
Article number7663
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number20
DOIs
Publication statusPublished - 16 Oct 2020
Publication type

Research output: Contribution to journalArticle

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.

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