1186例HLA基因与白血病相关性分析研究

Associations of HLA Gene with Leukemia in 1186 Cases

本研究探讨HLA-A、B、DRB1基因与3种常见白血病的相关性,采用序列特异性引物聚合酶链反应(polymerase chain reaction with sequence-specific primers,PCR-SSP)技术,对1186例的白血病患者(ALL 326例、AML 545例、CML 315例)进行HLA分型,与1234份健康非亲缘供者进行显著性比较,用Bonferroni校正法进行校正。结果表明:ALL患者组与对照组相比,HLA-DRB1*09的等位基因频率显著低于对照组(10.87%vs 16.08%;Pc=0.014,OR=0.637,95%CI=0.487-0.834);CML患者组与对照组相比,HLA-B*18的等位基因频率显著高于对照组(1.28%vs 0.20%;Pc=0.039,OR=6.336,95%CI=2.066-19.434)。某些HLA分子和白血病之间可能存在正相关和负相关。HLA-DRB1*09和ALL呈负相关表明,DRR1*09通过限制T细胞免疫反应在早期白血病性事件中起着重要作用;而HLA-B*18和CML呈正相关,提示B*18分子可能不主动呈递特异性白血病抗原,导致免疫逃逸。结论:本研究为临床对白血病的免疫治疗提供一些线索和思路。

The purpose of this study was to evaluate the potential associations between HLA-A, B, DRB1 gene and leukemia. A total of 1186 leukemic patients, including 326 patients with acute lymphoblastic leukemia （ALL）, 545 patients with acute myeloid leukemia （AML）, 315 patients with chronic myeloid leukemia （CML）, and 1234 healthy unrelated donors were typed and were compared in a single centre by using same technique, then the Bonferroni correction method was used to correct the Type I error. The results indicated that as compared with the control, the frequency of HLA-DRB1 ＊ 09 in ALL group significantly decreased （ 10.87 % versus 16.08 % ; Pc --0.014, OR = 0. 637, 95% CI = 0. 487 - 0. 834 ）, while in compadsion with control, the frequency of HLA-B＊ 18 in CML group was significanly higher （ 1.28% vs 0. 20% ; Pc = 0. 039, OR = 6. 336, 95% CI = 2. 066 - 19. 434 ）. The positive and negative relation may exist between certain HLA molecules and leukemia. The negative relation between HLA-DRB1 ＊ 09 and ALL indicated that DRB1 ＊ 09 might play an important role by a restricted T-cell immune response in the early leukemogenic events, whereas the positive relation between HLA-B ＊ 18 and CML suggests that the B ＊ 18 molecules may not actively present leukemia-specific antigens resulting in immune escape. It is concluded that these findings can contribute to developing more appropriate method in leukemic immunotherapy.