Zhen Jianxin, Yang Zhichao, Deng Zhihui
Central Laboratory, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, Guangdong 518133, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 May 10;39(5):499-504.
To investigate the association of molecular genetic polymorphism of KIR-HLA systems with acute lymphoblastic leukemia (ALL) and acute myelocytic leukemia (AML) in southern Chinese Han.
A total number of 323 cases of adult ALL patients, 350 adult AML, and 745 random healthy controls were tested by KIR PCR-SSP and HLA-A, -B, -C sequence-based typing (PCR-SBT) methods. The molecular genetic polymorphisms of KIR genes and KIR gene profiles, classⅠ HLA ligands, and KIR receptor +HLA ligand combinations were compared between patient and healthy control groups.
A total number of 32 and 33 different kinds of KIR profiles were identified in the ALL and AML patient groups. Compared with the observed frequencies of KIR profiles in healthy controls, the observed frequencies of KIR profile AA1 were significantly lower in both the ALL and AML groups (ALL group: 45.79% vs. 55.30%, Pc=0.004; AML group: 48.27% vs. 55.30%, Pc=0.030). In the ALL group, the observed frequencies of 2DL2 gene and 2DL2+HLA-C1 combination, 2DS2 gene and 2DS2+HLA-C1 combination were significantly higher than those in healthy controls (P<0.05), whereas the frequencies of 2DL3 gene, HLA-A3/A11 ligand and 3DL2+HLA-A3/A11 combination were significantly lower than those in healthy controls. However, no significant differences remained after Bonferroni correction (Pc>0.05). In AML group, the observed frequencies of both 2DS1 and 2DL5 genes were significantly higher than that in healthy controls, whereas the frequencies of HLA-C2 ligand and 2DL1+HLA-C2 combination were significantly lower than that in healthy controls(P<0.05). However, no significant difference existed after Bonferroni correction (Pc>0.05).
This study revealed some potential susceptibility or protective factors related to acute leukemia in southern Chinese Han, especially the protective factor KIR profile AA1, which might provide new clues and theoretical basis for the pathogenesis of acute leukemia and individualized immunotherapy.
探讨杀伤细胞免疫球蛋白样受体（KIR）-人类白细胞抗原（HLA）系统分子遗传多态性与中国南方汉族成人急性淋巴细胞白血病（ALL）和急性髓细胞白血病（AML）的相关性。
采用KIR聚合酶链反应-序列特异性引物（PCR-SSP）及基于HLA-A、-B、-C序列的分型（PCR-SBT）方法，检测323例成人ALL患者、350例成人AML患者及745名随机健康对照者。比较患者组与健康对照组KIR基因的分子遗传多态性、KIR基因谱、Ⅰ类HLA配体以及KIR受体+HLA配体组合情况。
在ALL和AML患者组中分别鉴定出32种和33种不同的KIR谱型。与健康对照组KIR谱型的观察频率相比，ALL组和AML组中KIR谱型AA1的观察频率均显著降低（ALL组：45.79%对55.30%，Pc = 0.004；AML组：48.27%对55.30%，Pc = 0.030）。在ALL组中，2DL2基因及2DL2+HLA-C1组合、2DS2基因及2DS2+HLA-C1组合的观察频率显著高于健康对照组（P<0.05），而2DL3基因、HLA-A3/A11配体及3DL2+HLA-A3/A11组合的频率显著低于健康对照组。然而，经Bonferroni校正后无显著差异（Pc>0.05）。在AML组中，2DS1和2DL5基因的观察频率均显著高于健康对照组，而HLA-C2配体及2DL1+HLA-C2组合的频率显著低于健康对照组（P<0.05）。经Bonferroni校正后无显著差异（Pc>0.05）。
本研究揭示了中国南方汉族人群中与急性白血病相关的一些潜在易感或保护因素，尤其是保护因素KIR谱型AA1，这可能为急性白血病的发病机制及个体化免疫治疗提供新的线索和理论依据。
