Weagel Evita G, Meng Wei, Townsend Michelle H, Velazquez Edwin J, Brog Rachel A, Boyer Michael W, Weber K Scott, Robison Richard A, O'Neill Kim L
Department of Microbiology and Molecular Biology, Brigham Young University, Provo.
Division of Hematology and Hematologic Malignancies, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Onco Targets Ther. 2017 Sep 6;10:4355-4367. doi: 10.2147/OTT.S141239. eCollection 2017.
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.
胸苷激酶1（TK1）是一种参与DNA合成与修复的酶。TK1通常在癌症患者血清中升高，这使其成为一种有用的肿瘤增殖生物标志物，与癌症分期、转移能力和复发风险密切相关。在本研究中，我们发现TK1在伯基特淋巴瘤、急性早幼粒细胞白血病、T细胞白血病和急性淋巴细胞白血病（ALL）的质膜上上调并定位。通过流式细胞术，我们证实TK1定位于Raji、HL60和Jurkat细胞系表面以及ALL临床样本上。利用荧光显微镜，我们发现TK1在Raji、HL60和Jurkat细胞系中与质膜有强烈关联。扫描电子显微镜也证实了这些发现。我们的研究还表明，这种现象在正常静息或增殖的淋巴细胞上不会发生。此外，我们发现膜TK1存在从单体到四聚体的所有寡聚形式，并具有酶活性。这些发现表明TK1可能是免疫治疗的一个靶点，有潜力用于血液系统癌症的治疗。
