Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies
Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies
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DOI：
10.1080/1042819021000035725
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发表时间：
2003-01-01
影响因子：
2.6
通讯作者：
Kawakami, Y
中科院分区：
文献类型：
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作者：
Matsushita, M;Yamazaki, R;Kawakami, Y
PRAME（黑色素瘤优先表达抗原）在多种实体肿瘤细胞和正常睾丸中高表达，最初是作为一种被细胞毒性T细胞（CTL）识别的人类黑色素瘤抗原被分离出来的。该基因也在一些血液系统恶性肿瘤中表达，包括急性髓系白血病（AML）和多发性骨髓瘤。我们及其他研究人员对PRAME在各种血液系统恶性肿瘤中的表达进行了广泛评估，并证明PRAME基因在AML、慢性髓系白血病、急性淋巴细胞白血病、淋巴瘤和多发性骨髓瘤的一些亚型中高表达。此外，我们已经证明PRAME是检测白血病患者微小残留病（MRD）的有用标志物，特别是对于那些目前没有肿瘤特异性标志物的白血病。由于PRAME最初被鉴定为一种被T细胞识别的肿瘤抗原，因此对PRAME是一种被T细胞识别的白血病抗原的可能性进行了评估，结果发现PRAME阳性白血病细胞系和新鲜白血病细胞易被PRAME特异性CTL裂解。最近已经鉴定出与HLA - A*0201或HLA - A*2402相关的5个CTL表位。因此，对处于MRD状态的PRAME阳性白血病患者应用PRAME特异性免疫疗法是一种很有吸引力的策略。
PRAME (Preferentially expressed antigen of melanoma), highly expressed in various solid tumor cells and normal testis, was first isolated as a human melanoma antigen recognized by cytotoxic T cells (CTL). This gene was also expressed in some of the hematological malignancies, including acute myelogenous leukemia (AML) and multiple myeloma. We and others have extensively evaluated the PRAME expression in various hematological malignancies and demonstrated high expression of the PRAME gene in subsets of AML, chronic myelogenous leukemia, acute lymphocytic leukemia, lymphoma and multiple myeloma. In addition, we have demonstrated that PRAME was a useful marker for detection of minimal residual disease (MRD) in patients with leukemia, particularly those leukemias in which tumor specific markers are currently unavailable. Since PRAME was first identified as a tumor antigen recognized by T cells, the possibility that PRAME is a leukemia antigen recognized by T cells was evaluated, and it was found that PRAME-positive leukemia cell lines and fresh leukemia cells were susceptible to lysis by the PRAME-specific CTL. Five CTL epitopes associated with either HLA-A*0201 or HLA-A*2402 have recently been identified. It is, therefore, an attractive strategy to apply PRAME specific immunotherapy on patients with PRAME positive leukemia in MRD condition.