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Brackertz, B.* ; Conrad, H.* ; Daniel, J.* ; Kast, B. ; Krönig, H.* ; Busch, D.H. ; Adamski, J. ; Peschel, C.* ; Bernhard, H.

FLT3-regulated antigens as targets for leukemia-reactive cytotoxic T lymphocytes.

Blood Cancer J. 1:e11 (2011)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The FMS-like tyrosine kinase 3 (FLT3) is highly expressed in acute myeloid leukemia (AML). Internal tandem duplications (ITD) of the juxtamembrane domain lead to the constitutive activation of the FLT3 kinase inducing the activation of multiple genes, which may result in the expression of leukemia-associated antigens (LAAs). We analyzed the regulation of LAA in FLT3-wild-type (WT)- and FLT3-ITD(+) myeloid cells to identify potential targets for antigen-specific immunotherapy for AML patients. Antigens, such as PR-3, RHAMM, Survivin, WT-1 and PRAME, were upregulated by constitutively active FLT3-ITD as well as FLT3-WT activated by FLT3 ligand (FL). Cytotoxic T-cell (CTL) clones against PR-3, RHAMM, Survivin and an AML-directed CTL clone recognized AML cell lines and primary AML blasts expressing FLT3-ITD, as well as FLT3-WT(+) myeloid dendritic cells in the presence of FL. Downregulation of FLT3 led to the abolishment of CTL recognition. Comparing our findings concerning LAA upregulation by the FLT3 kinase with those already made for the Bcr-Abl kinase, we found analogies in the LAA expression pattern. Antigens upregulated by both FLT3 and Bcr-Abl may be promising targets for the development of immunotherapeutical approaches against myeloid leukemia of different origin.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acute Myeloid Leukemia ; Flt3 Kinase ; Immunotherapy ; Leukemiaassociated Antigens ; T-cell Clones
e-ISSN 2044-5385
Zeitschrift Blood Cancer Journal
Quellenangaben Band: 1, Heft: 3, Seiten: , Artikelnummer: e11 Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
Molekulare Endokrinologie und Metabolismus (MEM)