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Lookup NU author(s): Dr Katarzyna SzoltysekORCiD, Dr Carmela Ciardullo, Dr Peixun Zhou, Dr Anna Walaszczyk, Dr Elaine WillmoreORCiD, Professor Vikki Rand, Dr Scott Marshall, Dr Andrew Hall, Professor Christine Harrison FRCPath FMedSci, Dr Jeyanthy Eswaran, Dr Meera Soundararajan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
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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