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TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment

Barbara Depreter, Karin Weening (UGent) , Karl Vandepoele (UGent) , Magnus Essand, Barbara De Moerloose (UGent) , Maria Themeli, Jacqueline Cloos, Diana Hanekamp, Ine Moors (UGent) , Inge D'hont (UGent) , et al.
(2020) HAEMATOLOGICA. 105(5). p.1306-1316
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Abstract
Immunotherapeutic strategies targeting the rare leukemic stem cell compartment might provide salvage to the high relapse rates currently observed in acute myeloid leukemia (AML). We applied gene expression profiling for comparison of leukemic blasts and leukemic stem cells with their normal counterparts. Here, we show that the T-cell receptor ? chain alternate reading frame protein (TARP) is over-expressed in de novo pediatric (n=13) and adult (n=17) AML sorted leukemic stem cells and blasts compared to hematopoietic stem cells and normal myeloblasts (15 healthy controls). Moreover, TARP expression was significantly associated with a Emslike tyrosine kinase receptor-3 internal tandem duplication in pediatric AML. TARP overexpression was confirmed in AML cell lines (n=9), and was found to be absent in B-cell acute lymphocytic leukemia (n=5) and chronic myeloid leukemia (n=1). Sequencing revealed that both a classical TARP transcript, as described in breast and prostate adenocarcinoma, and an AML-specific alternative TARP transcript, were present. Protein expression levels mostly matched transcript levels. TARP was shown to reside in the cytoplasmic compartment and showed sporadic endoplasmic reticulum co-localization. TARP-T-cell receptor engineered cytotoxic T-cells in vitro killed AML cell lines and patient leukemic cells co-expressing TARP and HLA-A*0201. In conclusion, TARP qualifies as a relevant target for immunotherapeutic T-cell therapy in AML.
Keywords
ALTERNATE READING FRAME, INTERNAL TANDEM DUPLICATION, PROTEIN TARP, T-LYMPHOCYTES, RECEPTOR, PROSTATE, DIAGNOSIS, RECOMMENDATIONS, MANAGEMENT, CHILDREN

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MLA
Depreter, Barbara, et al. “TARP Is an Immunotherapeutic Target in Acute Myeloid Leukemia Expressed in the Leukemic Stem Cell Compartment.” HAEMATOLOGICA, vol. 105, no. 5, 2020, pp. 1306–16, doi:10.3324/haematol.2019.222612.
APA
Depreter, B., Weening, K., Vandepoele, K., Essand, M., De Moerloose, B., Themeli, M., … Philippé, J. (2020). TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment. HAEMATOLOGICA, 105(5), 1306–1316. https://doi.org/10.3324/haematol.2019.222612
Chicago author-date
Depreter, Barbara, Karin Weening, Karl Vandepoele, Magnus Essand, Barbara De Moerloose, Maria Themeli, Jacqueline Cloos, et al. 2020. “TARP Is an Immunotherapeutic Target in Acute Myeloid Leukemia Expressed in the Leukemic Stem Cell Compartment.” HAEMATOLOGICA 105 (5): 1306–16. https://doi.org/10.3324/haematol.2019.222612.
Chicago author-date (all authors)
Depreter, Barbara, Karin Weening, Karl Vandepoele, Magnus Essand, Barbara De Moerloose, Maria Themeli, Jacqueline Cloos, Diana Hanekamp, Ine Moors, Inge D’hont, Barbara Denys, Anne Uyttebroeck, An Van Damme, Laurence Dedeken, SYLVIA SNAUWAERT, Glenn Goetgeluk, Stijn De Munter, Tessa Kerre, Bart Vandekerckhove, Tim Lammens, and Jan Philippé. 2020. “TARP Is an Immunotherapeutic Target in Acute Myeloid Leukemia Expressed in the Leukemic Stem Cell Compartment.” HAEMATOLOGICA 105 (5): 1306–1316. doi:10.3324/haematol.2019.222612.
Vancouver
1.
Depreter B, Weening K, Vandepoele K, Essand M, De Moerloose B, Themeli M, et al. TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment. HAEMATOLOGICA. 2020;105(5):1306–16.
IEEE
[1]
B. Depreter et al., “TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment,” HAEMATOLOGICA, vol. 105, no. 5, pp. 1306–1316, 2020.
@article{8634654,
  abstract     = {{Immunotherapeutic strategies targeting the rare leukemic stem cell compartment might provide salvage to the high relapse rates currently observed in acute myeloid leukemia (AML). We applied gene expression profiling for comparison of leukemic blasts and leukemic stem cells with their normal counterparts. Here, we show that the T-cell receptor ? chain alternate reading frame protein (TARP) is over-expressed in de novo pediatric (n=13) and adult (n=17) AML sorted leukemic stem cells and blasts compared to hematopoietic stem cells and normal myeloblasts (15 healthy controls). Moreover, TARP expression was significantly associated with a Emslike tyrosine kinase receptor-3 internal tandem duplication in pediatric AML. TARP overexpression was confirmed in AML cell lines (n=9), and was found to be absent in B-cell acute lymphocytic leukemia (n=5) and chronic myeloid leukemia (n=1). Sequencing revealed that both a classical TARP transcript, as described in breast and prostate adenocarcinoma, and an AML-specific alternative TARP transcript, were present. Protein expression levels mostly matched transcript levels. TARP was shown to reside in the cytoplasmic compartment and showed sporadic endoplasmic reticulum co-localization. TARP-T-cell receptor engineered cytotoxic T-cells in vitro killed AML cell lines and patient leukemic cells co-expressing TARP and HLA-A*0201. In conclusion, TARP qualifies as a relevant target for immunotherapeutic T-cell therapy in AML.}},
  author       = {{Depreter, Barbara and Weening, Karin and Vandepoele, Karl and Essand, Magnus and De Moerloose, Barbara and Themeli, Maria and Cloos, Jacqueline and Hanekamp, Diana and Moors, Ine and D'hont, Inge and Denys, Barbara and Uyttebroeck, Anne and Van Damme, An and Dedeken, Laurence and SNAUWAERT, SYLVIA and Goetgeluk, Glenn and De Munter, Stijn and Kerre, Tessa and Vandekerckhove, Bart and Lammens, Tim and Philippé, Jan}},
  issn         = {{0390-6078}},
  journal      = {{HAEMATOLOGICA}},
  keywords     = {{ALTERNATE READING FRAME,INTERNAL TANDEM DUPLICATION,PROTEIN TARP,T-LYMPHOCYTES,RECEPTOR,PROSTATE,DIAGNOSIS,RECOMMENDATIONS,MANAGEMENT,CHILDREN}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1306--1316}},
  title        = {{TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment}},
  url          = {{http://doi.org/10.3324/haematol.2019.222612}},
  volume       = {{105}},
  year         = {{2020}},
}
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