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Cancer‐testis antigen MAGEC 2 promotes proliferation and resistance to apoptosis in Multiple Myeloma
Author(s) -
Lajmi Nesrine,
Luetkens Tim,
Yousef Sara,
Templin Julia,
Cao Yanran,
Hildebrandt York,
Bartels Katrin,
Kröger Nicolaus,
Atanackovic Djordje
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13762
Subject(s) - multiple myeloma , cancer research , gene knockdown , apoptosis , small hairpin rna , biology , immunotherapy , gene silencing , cell cycle , cell growth , population , cancer , programmed cell death , immunology , medicine , immune system , gene , genetics , environmental health
Summary Cancer‐testis antigens belonging to the MAGE family of genes, such as MAGEC 2 , are commonly and specifically expressed in Multiple Myeloma ( MM ) and are associated with a more aggressive clinical course and chemotherapy resistance. MAGEC 2 is thought to be an excellent candidate for cancer immunotherapy; however, the biological role of MAGEC 2 in MM has remained unclear. We investigated the biological role of MAGEC 2 in myeloma cells determining the effect of MAGEC 2 knockdown on proliferation and apoptosis. Loss of MAGEC 2 resulted in reduced proliferation, viability, and anchorage‐independent growth of myeloma cells irrespective of the functional status of TP 53 (p53). The anti‐proliferative effect of MAGEC 2 silencing was due to a decrease of cells in the S phase, cell cycle delay at both G0/G1 and/or G2/M, and an increase in the sub‐G0/G1 diploid population related to apoptotic cell death. Importantly, overexpression of short hairpin (sh) RNA ‐refractory MAGEC 2 rescued the anti‐proliferative effect of mRNA knockdown and protected cells from apoptotic cell death. Our findings support a TP 53‐independent role of MAGEC 2 in promoting the survival of myeloma cells suggesting that MAGEC 2‐specific immunotherapies have the potential to eradicate the most malignant cells within the myeloma tumour bulk leading to durable clinical responses.