We have located links that may give you full text access.
Targeting the autophagy in bone marrow stromal cells overcomes resistance to vorinostat in chronic lymphocytic leukemia.
Background: The bone marrow microenvironment constitutes a sanctuary for leukemia cells. Recent evidence indicates that environment-mediated drug resistance arises from a reciprocal influence between tumor cells and the surrounding stroma. The present study aimed to investigate the effect of chronic lymphocytic leukemia (CLL) cells on the metabolism of bone marrow stroma, to determine the role of this metabolic change in the stroma in vorinostat resistance of CLL cells, and thus to assess a novel strategy to target stroma and achieve the maximum therapeutic effect of vorinostat.
Methods: To evaluate this issue, we used freshly isolated CLL cells from peripheral blood samples of patients with CLL, and co-cultured them with bone marrow stromal cell lines to examine autophagy activity and metabolic changes in both CLL cells and stromal cells after vorinostat treatment.
Results: The results demonstrated that CLL cells were under intrinsic oxidative stress which was further enhanced by vorinostat treatment, and released H2 O2 outside the cells. The adjacent stromal cells took up H2 O2 and drove autophagy, mitophagy and glycolysis, resulting in the local production of high-energy mitochondrial fuels, which were then taken up by CLL cells to be effectively utilized through mitochondrial oxidative phosphorylation to enable more ATP production. Notably, targeting autophagic stromal cells with autophagy inhibitor remarkably decreased stromal protection against vorinostat treatment in CLL cells.
Conclusion: This study demonstrated that the stroma in the CLL microenvironment is abnormal and undergoes autophagy, and manipulation of autophagic stromal cells could serve as a novel promising strategy to circumvent stroma-mediated drug resistance in CLL cells.
Methods: To evaluate this issue, we used freshly isolated CLL cells from peripheral blood samples of patients with CLL, and co-cultured them with bone marrow stromal cell lines to examine autophagy activity and metabolic changes in both CLL cells and stromal cells after vorinostat treatment.
Results: The results demonstrated that CLL cells were under intrinsic oxidative stress which was further enhanced by vorinostat treatment, and released H2 O2 outside the cells. The adjacent stromal cells took up H2 O2 and drove autophagy, mitophagy and glycolysis, resulting in the local production of high-energy mitochondrial fuels, which were then taken up by CLL cells to be effectively utilized through mitochondrial oxidative phosphorylation to enable more ATP production. Notably, targeting autophagic stromal cells with autophagy inhibitor remarkably decreased stromal protection against vorinostat treatment in CLL cells.
Conclusion: This study demonstrated that the stroma in the CLL microenvironment is abnormal and undergoes autophagy, and manipulation of autophagic stromal cells could serve as a novel promising strategy to circumvent stroma-mediated drug resistance in CLL cells.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app