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

Davis Jr, Warren; Tew, Kenneth D (2018) ATP-binding cassette transporter-2 (ABCA2) as a therapeutic target. Biochem Pharmacol 151:188-200
Mulligan, Jennifer K; Patel, Kunal; Williamson, Tucker et al. (2018) C3a receptor antagonism as a novel therapeutic target for chronic rhinosinusitis. Mucosal Immunol 11:1375-1385
Fernandes, Renata S; Silva, Juliana O; Mussi, Samuel V et al. (2018) Nanostructured Lipid Carrier Co-loaded with Doxorubicin and Docosahexaenoic Acid as a Theranostic Agent: Evaluation of Biodistribution and Antitumor Activity in Experimental Model. Mol Imaging Biol 20:437-447
Angel, Peggi M; Mehta, Anand; Norris-Caneda, Kim et al. (2018) MALDI Imaging Mass Spectrometry of N-glycans and Tryptic Peptides from the Same Formalin-Fixed, Paraffin-Embedded Tissue Section. Methods Mol Biol 1788:225-241
DeHart, David N; Fang, Diana; Heslop, Kareem et al. (2018) Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells. Biochem Pharmacol 148:155-162
Angel, Peggi M; Norris-Caneda, Kim; Drake, Richard R (2018) In Situ Imaging of Tryptic Peptides by MALDI Imaging Mass Spectrometry Using Fresh-Frozen or Formalin-Fixed, Paraffin-Embedded Tissue. Curr Protoc Protein Sci 94:e65
Zhang, Jie; Ye, Zhi-Wei; Singh, Shweta et al. (2018) An evolving understanding of the S-glutathionylation cycle in pathways of redox regulation. Free Radic Biol Med 120:204-216
Li, Xiaoyang; Peterson, Yuri K; Inks, Elizabeth S et al. (2018) Class I HDAC Inhibitors Display Different Antitumor Mechanism in Leukemia and Prostatic Cancer Cells Depending on Their p53 Status. J Med Chem 61:2589-2603
Kim, Mi Jin; Vargas, Marcelo R; Harlan, Benjamin A et al. (2018) Nitration and Glycation Turn Mature NGF into a Toxic Factor for Motor Neurons: A Role for p75NTR and RAGE Signaling in ALS. Antioxid Redox Signal 28:1587-1602
Fang, Diana; Maldonado, Eduardo N (2018) VDAC Regulation: A Mitochondrial Target to Stop Cell Proliferation. Adv Cancer Res 138:41-69

Showing the most recent 10 out of 109 publications