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Clar KL, Weber LM, Schmied BJ, et al. Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course. Cancers (Basel). 2021;13(23)doi: 10.3390/cancers13236122.
Clar, K. L., Weber, L. M., Schmied, B. J., Heitmann, J. S., Marconato, M., Tandler, C., Schneider, P., & Salih, H. R. (2021). Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course. Cancers, 13(23), . https://doi.org/10.3390/cancers13236122
Clar, Kim L, et al. "Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course." Cancers vol. 13,23 (2021). doi: https://doi.org/10.3390/cancers13236122
Clar KL, Weber LM, Schmied BJ, Heitmann JS, Marconato M, Tandler C, Schneider P, Salih HR. Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course. Cancers (Basel). 2021 Dec 04;13(23). doi: 10.3390/cancers13236122. PMID: 34885231; PMCID: PMC8657109.
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Cancers (Basel). 2021 Dec 04;13(23). doi: 10.3390/cancers13236122.

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

Cancers

Kim L Clar, Lisa M Weber, Bastian J Schmied, Jonas S Heitmann, Maddalena Marconato, Claudia Tandler, Pascal Schneider, Helmut R Salih

Affiliations

  1. Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Department of Internal Medicine, University Hospital Tuebingen, 72076 Tuebingen, Germany.
  2. DFG Cluster of Excellence 2180 "Image-Guided and Functional Instructed Tumor Therapy (iFIT)", University of Tuebingen, 72076 Tuebingen, Germany.
  3. Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.

PMID: 34885231 PMCID: PMC8657109 DOI: 10.3390/cancers13236122

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

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