Shen Meixin, Linn Yeh-Ching, Ren Ee-Chee
Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos #03-06, Singapore, 138648, Singapore.
Department of Haematology, Singapore General Hospital, Academia, 20 College Road, Singapore, 169856, Singapore.
Immunogenetics. 2016 Feb;68(2):133-44. doi: 10.1007/s00251-015-0888-4. Epub 2015 Dec 9.
The expression and interaction between killer cell immunoglobulin-like receptors (KIRs) and HLA are known to be associated with pathogenesis of diseases, including hematological malignancies. Presence of B haplotype KIR in donors is associated with a lower relapse risk for acute myeloid leukemia (AML) after hematopoietic stem cell transplants (HSCT). However, the association of KIR and HLA repertoire with disease development and other clinical features is not well studied for AML. In this study, 206 Chinese patients with AML were analyzed for their FAB subtypes, risk groups, and chemo-responsiveness to assess possible association with their KIR and HLA profile. The results revealed that a B-content score of 2 was significantly more prevalent in AML patients when compared to normal controls. Notably, there is also a differential frequency in the distribution of B haplotype KIR across distinct FAB subtypes, where the M3 subtype had significantly lower frequencies of B haplotype KIR compared to the M5 subtype (p < 0.05). In addition, the stronger inhibitory KIR ligands HLA-C2 and HLA-Bw4-80I were present in significantly higher frequencies in the prognostically "poor" risk group compared to those with "favourable" risk (p < 0.01). Taken together, these associations with clinical features of AML suggest a role of the KIR-HLA repertoire in the development and biological behavior of AML.
已知杀伤细胞免疫球蛋白样受体(KIR)与人类白细胞抗原(HLA)之间的表达及相互作用与包括血液系统恶性肿瘤在内的多种疾病的发病机制相关。供体中存在B单倍型KIR与造血干细胞移植(HSCT)后急性髓系白血病(AML)的较低复发风险相关。然而,对于AML,KIR和HLA库与疾病发展及其他临床特征之间的关联尚未得到充分研究。在本研究中,对206例中国AML患者的FAB亚型、风险组及化疗反应性进行了分析,以评估其与KIR和HLA谱的可能关联。结果显示,与正常对照相比,AML患者中B含量评分为2的情况明显更为普遍。值得注意的是,不同FAB亚型中B单倍型KIR的分布频率也存在差异,其中M3亚型的B单倍型KIR频率明显低于M5亚型(p<0.05)。此外,与“有利”风险组相比,预后“不良”风险组中更强的抑制性KIR配体HLA-C2和HLA-Bw4-80I的频率明显更高(p<0.01)。综上所述,这些与AML临床特征的关联表明KIR-HLA库在AML的发生发展及生物学行为中发挥作用。