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

被引:0
|
作者
B Brackertz
H Conrad
J Daniel
B Kast
H Krönig
D H Busch
J Adamski
C Peschel
H Bernhard
机构
[1] Klinikum rechts der Isar,Department of Hematology/Oncology
[2] Technische Universit,Department of Hematology/Oncology
[3] ä,undefined
[4] t M,undefined
[5] ü,undefined
[6] nchen,undefined
[7] Clinical Cooperation Group ‘Antigen-Specific Immunotherapy’ Helmholtzzentrum M,undefined
[8] ü,undefined
[9] nchen,undefined
[10] German Research Center for Environmental Health,undefined
[11] Institute of Medical Microbiology,undefined
[12] Immunology and Hygiene,undefined
[13] Technische Universit,undefined
[14] ä,undefined
[15] t M,undefined
[16] ü,undefined
[17] nchen,undefined
[18] Institute of Experimental Genetics,undefined
[19] Genome Analysis Center,undefined
[20] Helmholtz Zentrum M,undefined
[21] ü,undefined
[22] nchen,undefined
[23] German Research Center for Environmental Health,undefined
[24] Institute of Experimental Genetics,undefined
[25] Life and Food Science Center Weihenstephan,undefined
[26] Technische Universit,undefined
[27] ä,undefined
[28] t M,undefined
[29] ü,undefined
[30] nchen,undefined
[31] Klinikum Darmstadt GmbH,undefined
来源
Blood Cancer Journal | 2011年 / 1卷
关键词
acute myeloid leukemia; FLT3 kinase; leukemia-associated antigens; T-cell clones; immunotherapy;
D O I
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学科分类号
摘要
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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页码:e11 / e11
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