Protein kinase C-β-dependent changes in the glucose metabolism of bone marrow stromal cells of chronic lymphocytic leukemia

Von Heydebrand F, Fuchs M, Kunz M, Kremer A, Oostendorp RAJ, Wilke J, Leitges M, Egle A, Mackensen A, Lutzny-Geier G, Völkl S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Stem Cells AlphaMed Press

DOI: 10.1002/stem.3352

Abstract

Survival of chronic lymphocytic leukemia (CLL) cells critically depends on the support of an adapted and therefore appropriate tumor microenvironment. Increasing evidence suggests that B-cell receptor-associated kinases such as protein kinase C-β (PKCβ) or Lyn kinase are essential for the formation of a microenvironment supporting leukemic growth. Here, we describe the impact of PKCβ on the glucose metabolism in bone marrow stromal cells (BMSC) upon CLL contact. BMSC get activated by CLL contact expressing stromal PKCβ that diminishes mitochondrial stress and apoptosis in CLL cells by stimulating glucose uptake. In BMSC, the upregulation of PKCβ results in increased mitochondrial depolarization and leads to a metabolic switch toward oxidative phosphorylation. In addition, PKCβ-deficient BMSC regulates the expression of Hnf1 promoting stromal insulin signaling after CLL contact. Our data suggest that targeting PKCβ and the glucose metabolism of the leukemic niche could be a potential therapeutic strategy to overcome stroma-mediated drug resistance.

Authors with CRIS profile

Maximilian Fuchs Lehrstuhl für Medizinische Informatik Meik Kunz Lehrstuhl für Medizinische Informatik Anita Kremer Department of Medicine 5 – Haematology and Oncology Andreas Mackensen Lehrstuhl für Innere Medizin V Gloria Lutzny-Geier Department of Medicine 5 – Haematology and Oncology Simon Völkl Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Memorial University of Newfoundland (MUN) CA Canada (CA) Paracelsus Medizinische Privatuniversität AT Austria (AT) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Von Heydebrand, F., Fuchs, M., Kunz, M., Kremer, A., Oostendorp, R.A.J., Wilke, J.,... Völkl, S. (2021). Protein kinase C-β-dependent changes in the glucose metabolism of bone marrow stromal cells of chronic lymphocytic leukemia. Stem Cells. https://doi.org/10.1002/stem.3352

MLA:

Von Heydebrand, Franziska, et al. "Protein kinase C-β-dependent changes in the glucose metabolism of bone marrow stromal cells of chronic lymphocytic leukemia." Stem Cells (2021).

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