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Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia

Authors Weagel EG, Meng W, Townsend MH, Velazquez EJ, Brog RA, Boyer MW, Weber KS, Robison RA, O'Neill KL

Received 6 May 2017

Accepted for publication 3 August 2017

Published 6 September 2017 Volume 2017:10 Pages 4355—4367

DOI https://doi.org/10.2147/OTT.S141239

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly

Evita G Weagel,1 Wei Meng,1 Michelle H Townsend,1 Edwin J Velazquez,1 Rachel A Brog,1 Michael W Boyer,2 K Scott Weber,1 Richard A Robison,1 Kim L O’Neill1

1Department of Microbiology and Molecular Biology, Brigham Young University, Provo, 2Division of Hematology and Hematologic Malignancies, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

Abstract: TK1 is an enzyme involved in DNA synthesis and repair. TK1 is usually found elevated in cancer patients’ serum, which makes it a useful tumor proliferation biomarker that strongly correlates with cancer stage, metastatic capabilities, and recurrence risk. In this study, we show that TK1 is upregulated and localizes on the plasma membrane of Burkitt’s lymphoma, acute promyelocytic leukemia, T cell leukemia, and acute lymphoblastic leukemia (ALL). Using flow cytometry, we confirmed that TK1 localizes on the surface of Raji, HL60, and Jurkat cell lines and on ALL clinical samples. Using fluorescent microscopy, we found a strong association of TK1 with the plasma membrane in Raji, HL60, and Jurkat cell lines. These findings were also confirmed by scanning electron microscopy. Our study also shows that this phenomenon does not occur on normal resting or proliferating lymphocytes. In addition, we show that membrane TK1 is found in all oligomeric forms ranging from monomer to tetramer and exhibits enzymatic activity. These findings suggest TK1 as a possible target for immunotherapy with the potential to be utilized in the treatment of hematological cancers.

Keywords: Burkitt’s lymphoma, acute lymphoblastic leukemia, ALL, thymidine kinase 1, surface antigen

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Non-small-cell lung cancer cell lines A549 and NCI-H460 express hypoxanthine guanine phosphoribosyltransferase on the plasma membrane

Townsend MH, Anderson MD, Weagel EG, Velazquez EJ, Weber KS, Robison RA, O'Neill KL

OncoTargets and Therapy 2017, 10:1921-1932

Published Date: 30 March 2017