Premium
Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia
Author(s) -
Atanackovic Djordje,
Luetkens Tim,
Kloth Benjamin,
Fuchs Gregor,
Cao Yanran,
Hildebrandt York,
Meyer Sabrina,
Bartels Katrin,
Reinhard Henrike,
Lajmi Nesrine,
HegewischBecker Susanna,
Schilling Georgia,
Platzbecker Uwe,
Kobbe Guido,
Schroeder Thomas,
Bokemeyer Carsten,
Kröger Nicolaus
Publication year - 2011
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.22141
Subject(s) - demethylating agent , myeloid leukemia , cancer research , azacitidine , medicine , immunotherapy , myeloid , cancer , antigen , decitabine , oncology , immunology , dna methylation , biology , gene expression , gene , genetics
Cancer‐testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor‐restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE‐A3, PRAME, ROPN1, SCP‐1, SLLP1, and SPO11) with an AML‐restricted expression. Analyzing the expression of these CTA in blast‐containing samples from AML patients ( N = 64), we found all samples to be negative for MAGE‐A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP‐1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5′‐aza‐2′‐deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX‐2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX‐2 after demethylating therapy with 5‐azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX‐2, in vitro and in vivo. Therefore, we propose that CTA‐specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX‐2. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.