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Dap kinase-related apoptosis-inducing protein kinase 2 (Drak2) is a key regulator and molecular marker in chronic lymphocytic leukemia

Lookup NU author(s): Dr Katarzyna Szoltysek, Dr Carmela Ciardullo, Dr Peixun Zhou, Dr Anna Walaszczyk, Dr Elaine Willmore, Professor Vikki Rand, Dr Scott Marshall, Emeritus Professor Andy Hall, Professor Christine Harrison FRCPath FMedSci, Dr Jeyanthy Eswaran, Dr Meera Soundararajan

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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.


Publication metadata

Author(s): Szoltysek K, Ciardullo C, Zhou P, Walaszczyk A, Willmore E, Rand V, Marshall S, Hall A, Harrison CJ, Eswaran J, Soundararajan M

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2020

Volume: 21

Issue: 20

Online publication date: 16/10/2020

Acceptance date: 14/10/2020

Date deposited: 30/12/2020

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: MDPI AG

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

DOI: 10.3390/ijms21207663

PubMed id: 33081245


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