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

Szoltysek, Katarzyna, Ciardullo, Carmela, Zhou, Peixun, Walaszczyk, Anna, Willmore, Elaine, Rand, Vikki, Marshall, Scott, Hall, Andy, J. Harrison, Christine, Eswaran, Jeyanthy and Soundararajan, Meera (2020) DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences, 21 (20). p. 7663. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms21207663


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.

Item Type: Article
Additional Information: Funding information: Funding: This study was supported by research funding from JGW Patterson Foundation (grant No: 116689), and Marie Curie International Incoming Fellowship (Grant No: PIIF-GA-2013-626749).
Uncontrolled Keywords: CLL; DRAK2; STK17B; prognostic indicator; DAPK1
Subjects: A300 Clinical Medicine
B200 Pharmacology, Toxicology and Pharmacy
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 16 Oct 2020 11:32
Last Modified: 01 Sep 2021 11:13
URI: http://nrl.northumbria.ac.uk/id/eprint/44534

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