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

Depreter, Barbara (författare)
Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium.;Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.
Weening, Karin E. (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Univ Ghent, Dept Diagnost Sci, Ghent, Belgium.
Vandepoele, Karl (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Ghent Univ Hosp, Dept Lab Med, Ghent, Belgium.
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Essand, Magnus (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
De Moerloose, Barbara (författare)
Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium.;Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Ghent, Belgium.
Themeli, Maria (författare)
Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands.
Cloos, Jacqueline (författare)
Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands.
Hanekamp, Diana (författare)
Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands.
Moors, Ine (författare)
Ghent Univ Hosp, Dept Hematol, Ghent, Belgium.
D'hont, Inge (författare)
Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Ghent, Belgium.
Denys, Barbara (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Ghent Univ Hosp, Dept Lab Med, Ghent, Belgium.
Uyttebroeck, Anne (författare)
Univ Hosp Gasthuisberg, Dept Pediat, Louvain, Belgium.
Van Damme, An (författare)
Univ Hosp St Luc, Dept Pediat Hematol Oncol, Brussels, Belgium.
Dedeken, Laurence (författare)
Queen Fabiola Childrens Univ Hosp, Dept Pediat Hematol Oncol, Brussels, Belgium.
Snauwaert, Sylvia (författare)
AZ Sint Jan Hosp Bruges, Dept Hematol, Brugge, Belgium.
Goetgeluk, Glenn (författare)
Univ Ghent, Dept Diagnost Sci, Ghent, Belgium.
De Munter, Stijn (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Univ Ghent, Dept Diagnost Sci, Ghent, Belgium.
Kerre, Tessa (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Ghent Univ Hosp, Dept Hematol, Ghent, Belgium.
Vandekerckhove, Bart (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Univ Ghent, Dept Diagnost Sci, Ghent, Belgium.
Lammens, Tim (författare)
Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium.;Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.
Philippe, Jan (författare)
Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Univ Ghent, Dept Diagnost Sci, Ghent, Belgium.;Ghent Univ Hosp, Dept Lab Med, Ghent, Belgium.
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Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium;Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium. Univ Ghent, Canc Res Inst Ghent, Ghent, Belgium.;Univ Ghent, Dept Diagnost Sci, Ghent, Belgium. (creator_code:org_t)
2019-08-01
2020
Engelska.
Ingår i: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 105:5, s. 1306-1316
Relaterad länk:
https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
https://haematologic...
https://urn.kb.se/re...
https://doi.org/10.3...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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