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

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 upregulat...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593407/
https://www.ncbi.nlm.nih.gov/pubmed/28919785
http://dx.doi.org/10.2147/OTT.S141239
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author 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
author_facet 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
author_sort Weagel, Evita G
collection PubMed
description 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.
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spelling pubmed-55934072017-09-15 Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia 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 Onco Targets Ther Original Research 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. Dove Medical Press 2017-09-06 /pmc/articles/PMC5593407/ /pubmed/28919785 http://dx.doi.org/10.2147/OTT.S141239 Text en © 2017 Weagel et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
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
Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia
title Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia
title_full Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia
title_fullStr Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia
title_full_unstemmed Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia
title_short Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia
title_sort biomarker analysis and clinical relevance of tk1 on the cell membrane of burkitt’s lymphoma and acute lymphoblastic leukemia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593407/
https://www.ncbi.nlm.nih.gov/pubmed/28919785
http://dx.doi.org/10.2147/OTT.S141239
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