Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B23D9F7E88BF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course.
Journal
Cancers
Author(s)
Clar K.L., Weber L.M., Schmied B.J., Heitmann J.S., Marconato M., Tandler C., Schneider P., Salih H.R.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
04/12/2021
Peer-reviewed
Oui
Volume
13
Number
23
Pages
6122
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Although treatment options of acute myeloid leukemia (AML) have improved over the recent years, prognosis remains poor. Better understanding of the molecular mechanisms influencing and predicting treatment efficacy may improve disease control and outcome. Here we studied the expression, prognostic relevance and functional role of the tumor necrosis factor receptor (TNFR) family member Receptor Activator of Nuclear Factor (NF)-κB (RANK) in AML. We conducted an experimental ex vivo study using leukemic cells of 54 AML patients. Substantial surface expression of RANK was detected on primary AML cells in 35% of the analyzed patients. We further found that RANK signaling induced the release of cytokines acting as growth and survival factors for the leukemic cells and mediated resistance of AML cells to treatment with doxorubicin and cytarabine, the most commonly used cytostatic compounds in AML treatment. In line, RANK expression correlated with a dismal disease course as revealed by reduced overall survival. Together, our results show that RANK plays a yet unrecognized role in AML pathophysiology and resistance to treatment, and identify RANK as "functional" prognostic marker in AML. Therapeutic modulation of RANK holds promise to improve treatment response in AML patients.
Keywords
AML, RANK, chemotherapy resistance, cytarabine, doxorubicin, prognosis
Pubmed
Web of science
Open Access
Yes
Create date
20/12/2021 13:41
Last modification date
08/01/2022 6:33
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