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

Abstract

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

Keywords

• Burkitt’s lymphoma
• acute lymphoblastic leukemia
• ALL
• thymidine kinase 1
• surface antigen