Abstract

Cyclin D3 and cyclin-dependent kinases 6(CDK6) are components of the core cell cycle machinery driving cell proliferation, and generally amplified in T acute lymphoblastic leukemia (T-ALL). The pro-survival function of cyclin D3/CDK6 in T-ALL cells via phosphorylating/inactivating PFKP and PKM2 (two key enzymes in glycolysis) is recently addressed. Targeting cyclin D3/CDK6 is a promising method for T-ALL therapy. As tumor microenvironment cell play critical roles in regulating tumor progression, it is critical/urgent to understand the functions of cyclin D3/CDK6 in tumor microenvironment cells. Our preliminary study showed that cyclin D3/CDK6 expression was significantly upregulated in T cells under activation condition. Ablation of cyclin D3 or CFK6 dramatically decreased regulatory T cell (Tregs) population without inducing cell apoptosis. Tregs promote tumor progression by inhibiting T help cells and CD8+ cytotoxic T cells. We therefore hypothesized that cyclin D3/CDK6 regulate T-ALL progression via T-ALL prosurvival and Tregs differentiation. This study will provide the rational to treat T-ALL by targeting cyclin D3/CDK6.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103542-10
Application #
10244667
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Gao, Hongwei
Project Start
2020-08-01
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
10
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29407

  Publications

Gibbs, Whitney S; Garrett, Sara M; Beeson, Craig C et al. (2018) Identification of dual mechanisms mediating 5-hydroxytryptamine receptor 1F-induced mitochondrial biogenesis. Am J Physiol Renal Physiol 314:F260-F268
Nunes, Shirleide Santos; Fernandes, Renata Salgado; Cavalcante, Carolina Henriques et al. (2018) Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes. Drug Deliv Transl Res :
Monteiro, Liziane O F; Fernandes, Renata S; Oda, Caroline M R et al. (2018) Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study. Biomed Pharmacother 97:489-495
Womersley, Jacqueline S; Townsend, Danyelle M; Kalivas, Peter W et al. (2018) Targeting redox regulation to treat substance use disorder using N-acetylcysteine. Eur J Neurosci :
Herr, Daniel J; Baarine, Mauhamad; Aune, Sverre E et al. (2018) HDAC1 localizes to the mitochondria of cardiac myocytes and contributes to early cardiac reperfusion injury. J Mol Cell Cardiol 114:309-319
Angel, Peggi M; Comte-Walters, Susana; Ball, Lauren E et al. (2018) Mapping Extracellular Matrix Proteins in Formalin-Fixed, Paraffin-Embedded Tissues by MALDI Imaging Mass Spectrometry. J Proteome Res 17:635-646
Hedges, David M; Obray, J Daniel; Yorgason, Jordan T et al. (2018) Methamphetamine Induces Dopamine Release in the Nucleus Accumbens Through a Sigma Receptor-Mediated Pathway. Neuropsychopharmacology 43:1405-1414
Ramshesh, Venkat K; Lemasters, John J (2018) Imaging of Mitochondrial pH Using SNARF-1. Methods Mol Biol 1782:351-356
DeHart, David N; Lemasters, John J; Maldonado, Eduardo N (2018) Erastin-Like Anti-Warburg Agents Prevent Mitochondrial Depolarization Induced by Free Tubulin and Decrease Lactate Formation in Cancer Cells. SLAS Discov 23:23-33
Mazza, Alberto; Lenti, Salvatore; Schiavon, Laura et al. (2018) Effect of Monacolin K and COQ10 supplementation in hypertensive and hypercholesterolemic subjects with metabolic syndrome. Biomed Pharmacother 105:992-996

Showing the most recent 10 out of 109 publications