mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies
mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies
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DOI：
10.1002/ijc.11623
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发表时间：
2004-02-20
影响因子：
6.4
通讯作者：
Schmitt, M
中科院分区：
文献类型：
--
作者：
Greiner, J;Ringhoffer, M;Schmitt, M
使用白血病相关抗原（LAA）作为靶结构的急性髓性白血病（AML）患者的特异性免疫疗法可能是一种治疗选择，以增强移植物抗白血病的能力。异基因干细胞移植后观察到的白血病效应或延长通过化疗实现的完全缓解（CR）。LAA的显著mRNA表达是这种免疫疗法的先决条件。在这里，先前表征的抗原与实体瘤（TAA）和新表征的LAA进行了研究，其表达在多达60例AML患者和白血病细胞系。为了研究它们对白血病原始细胞的特异性，还在健康志愿者的PBMN和CD 34阳性细胞以及一组正常组织中表征了mRNA表达。在AML患者中，以下抗原显示高mRNA表达：MPP II在43/50（86%）中检测到，RHAMM在35/50（70%）中检测到，WTI在40/60（67%）中检测到，PRAME在32/50（64%）中检测到，G250在18/35（51%）中检测到，hTERT在7/25（28%）中检测到，巴格在8/30（27%）的AML患者中检测到。Real-time RT-PCR显示巴格、G250和hTERT抗原的肿瘤特异性表达，以及RHAMM、PRAME和WTI的高度肿瘤限制性表达。MPP Ⅱ抗原过表达。这些抗原可能是白血病患者免疫治疗的候选者，并且由于它们的同时表达，也可能是多价疫苗的候选者。(C)2003 Wiley-Liss，Inc.
Specific immunotherapies for patients with acute myeloid leukemia (AML) using leukemia-associated antigens (LAA) as target structures might be a therapeutic option to enhance the graft-vs.-leukemia effect observed after allogeneic stem cell transplantation or to prolong a complete remission (CR) achieved by chemotherapy. Significant mRNA expression of LAA is a prerequisite for such immunotherapies. Here, previously characterized antigens associated with solid tumors (TAA) and newly characterized LAA were investigated for their expression in up to 60 AML patients and in leukemia cell lines. To investigate their specificity for leukemic blasts, the mRNA expression was also characterized in PBMN and CD34 positive cells of healthy volunteers and in a panel of normal tissues. The following antigens showed high mRNA expression in AML patients: MPP II was detected in 43/50 (86%), RHAMM in 35/50 (70%), WTI in 40/60 (67%), PRAME in 32/50 (64%), G250 in 18/35 (51%), hTERT in 7/25 (28%) and BAGE in 8/30 (27%) of AML patients. Real-time RT-PCR showed a tumor-specific expression of the antigens BAGE, G250 and hTERT, as well as highly tumor-restricted expression for RHAMM, PRAME and WTI. The antigen MPP II was overexpressed. These antigens might be candidates for immunotherapies of leukemia patients and, because of their simultaneous expression, also for polyvalent vaccines. (C) 2003 Wiley-Liss, Inc.