MAGE‐1 gene is expressed in T‐cell leukemia

MAG51 gene codes for tumor antigens on HLA-AI, -Cw1601 and, probably, -A2 (Van der Bruggen et al., 1991, I994b; Celis et al., 1994). A family of 12 closely related MAGE genes is located on chromosome X (De Plaen et al., 1994). Among them, the MAGE-I, -2, -3, -4, -6 and -12 genes are preferentially expressed in many different solid cancers. In contrast to extensive studies of solid cancers, MAGE gene expression in hematological malignancies has not been fully investigated. It was initially reported that none of 48 leukemias (28 myelogenous, 14 lymphocytic and 6 other types) expressed MAGE-I mRNA (Chambost et al., 1993). We have reported expression of the MAGE gene family in a substantial number of T-cell leukemias as evaluated by the primers common to the MAGE-I, -2, -3, -4 and -6 genes (Shichijo et al., 1995a). However, the specific MAGE gene(s) in T-cell leukemia was not identified. This letter reports that the MAGE-1 gene is preferentially expressed in T-cell leukemia. Heparinized peripheral blood was collected from 49 leukemia patients admitted to the First Department of Internal Medicine, Kurume University School of Medicine, and 2 leukemia patients from the Department of Internal Medicine, Miyazaki Prefectural Hospital. Su$ace markers of patients' PBMC were studied by flow cytometric analysis using various monoclonal antibodies (MAbs), including anti-CD3, anti-CDI 9, antiCD14 and anti-HLA class I MAbs (W6132) (Becton Dickinson, Mountain View, CA). These 51 patients were diagnosed as follows: 23 T-cell leukemias (19 adult T-cell leukemias [ATL], 2 chronic T-cell lymphocytic leukemias [CTLL], 1 acute prolymphocytic leukemia [APL] and I acute lymphocytic leukemia [ALL]), I I B-cell leukemias (8 acute lymphocytic leukemias [ALL] and 3 chronic lymphocytic leukemias [CLL]) and 17 myeloid-monocytic leukemias (12 acute myelocytic leukemias [AML], 3 chronic myelocytic leukemias [CML], 2 acute monocytic leukemias [AMoL] and 1 acute myeloidmonocytic leukemia [AMMoL]). These PBMCs, consisting of more than 50% leukemia cells, were collected prior to treatments and cryopresewed in a liquid nitrogen tank at -130°C until use. PBMCs from these patients were tested for expression of MAGE-I, -2, -3, -4 and -6genes at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and oligonucleotide primers specific to each of the MAGE genes as reported (De Plaen et al., 1994). The results of MAGE-I expression in T-cell leukemia are shown in Figure 1. Summarized results are shown in Table I. MAGE-I, -2, -3, -4 or -6 genes were expressed in 12, 3, 2, 0 or 2 of 23 T-cell leukemias, respectively. Twelve MAGE-I+ tumors consisted of 10 of 19 ATL, 1 of 2 CTLL, I of 1 ALL and 0 of I APL. Eight of 12 MAGE-I + T-cell leukemias expressed the MAGE-I gene solely. The other 4 MAGE-I + T-cell leukemias co-expressed the other MAGE genes. In contrast, none of 12 B-cell leukemias, except for I CLL, expressed any MAGE gene tested. None of 17 myeloid-monocyte leukemias expressed any MAGE-I, -2, -3 or -4 genes. Four myeloid-monocytic leukemias expressed MAGE-6 gene solely. Our present results show that approximately half of human T-cell leukemia cases express the MAGE-I gene. Substantial proportions of human solid cancers usually express not only MAGE-1 but the other related genes of the MAGE family either within I tumor or in different tumors with an identical histology (Van derBruggen et al., 1991, 1994a; Shichijo et al., 1995b). In contrast, 8 of 12 MAGE-I+ T-cell leukemia cases solely expressed MAGE-1 gene. In particular, 7 of these 8 leukemia cases were ATL. Mechanisms of such preferential expression of the MAGE-1 gene in T-cell leukemia are presently unknown. The major@ of the cells of these T-cell leukemias expressed appropriate levels of HLA-class I antigens as evaluated by W6132 anti-class I MAb and immunofluorescent analysis (data not shown). In contrast, MAGE-I was rarely or not at all expressed in B-cell leukemia or myeloid-monocytic leukemia, respectively. Our results suggest that the MAGE-I gene product is an appropriate target molecule for specific immunotherapy of a substantial number of T-cell leukemias. This information is important for specific immunotherapy of leukemia with the MAGE-I gene product. Yours sincerely, Shigeki S H I C H I J ~ , Kimitaka SAGAWA', Francis BRASSEUR~, Thieny Boohi2 and Kyogo I T O ~ IDepartment of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830, Japan; 2Ludwig Institute for Cancer Research, 74 avenue Hippocrate, 1200 Brussels, Belgium.