Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Sci Rep. 2019 Sep 24;9(1):13731. doi: 10.1038/s41598-019-50111-5.
Disease relapse occurs in patients with leukemia even hematopoietic stem cell transplantation (HSCT) was performed with human leukocyte antigen (HLA)-matched donors. As revealed previously by Petersdorf et al., there are nine single nucleotide polymorphisms (SNPs) located in the HLA region that potentially modulate the efficacy of HSCT. In this study, we investigated whether or not the genomic variants 500 base pairs flanking the nine transplantation-related SNPs were related to the risk of post-HSCT relapse for patients with leukemia (n = 141). The genomic DNAs collected from 85 patients with acute myeloid leukemia (AML), 56 patients with acute lymphocytic leukemia (ALL), and their respective HLA-matched donors were subject to SNPs analysis, conferred by the mode of mismatch between donor-recipient pair or by recipient or donor genotype analysis. Seven SNPs were revealed to associate with the risk of relapse post-HSCT. For patients with AML, the increased risk of post-HSCT relapse was associated with the donor SNP of rs111394117 in the intron of NOTCH4 gene, and the recipient SNPs of rs213210 in the ring finger protein 1 (RING1) gene promoter, and rs17220087 and rs17213693 in the intron of HLA-DOB gene. For patients with ALL, the increased risk of post-HSCT relapse was associated with the donor SNP of rs213210 in the RING1 gene promoter, and the recipient SNPs of rs79327197 in the HLA-DOA gene promoter, rs2009658 in the telomeric end of lymphotoxin-alpha (LTA) gene, rs17220087 and rs17213693 in the intron of HLA-DOB gene, and rs2070120 in the 3'-UTR of HLA-DOB gene. This study sheds new insight into selecting better candidate donors for performing HSCT in patients with AML and ALL.
即使使用与人类白细胞抗原 (HLA) 匹配的供体进行造血干细胞移植 (HSCT)，白血病患者仍会出现疾病复发。正如 Petersdorf 等人之前所揭示的那样，HLA 区域存在九个单核苷酸多态性 (SNP)，这些 SNP 可能调节 HSCT 的疗效。在这项研究中，我们研究了白血病患者 (n=141) 中位于九个移植相关 SNP 侧翼的 500 个碱基对的基因组变异是否与 HSCT 后复发的风险相关。从 85 例急性髓细胞白血病 (AML) 患者、56 例急性淋巴细胞白血病 (ALL) 患者及其各自的 HLA 匹配供体中收集基因组 DNA，进行 SNP 分析，通过供体-受者对之间的错配模式或受者或供体基因型分析来推断 SNP。揭示了七个 SNP 与 HSCT 后复发的风险相关。对于 AML 患者，HSCT 后复发的风险增加与 NOTCH4 基因内含子中的供体 SNP rs111394117、RING1 基因启动子中的受者 SNP rs213210 以及 HLA-DOB 基因内含子中的 rs17220087 和 rs17213693 相关。对于 ALL 患者，HSCT 后复发的风险增加与 RING1 基因启动子中的供体 SNP rs213210、HLA-DOA 基因启动子中的受者 SNP rs79327197、淋巴毒素-α (LTA) 基因端粒末端的 rs2009658、HLA-DOB 基因内含子中的 rs17220087 和 rs17213693 以及 HLA-DOB 基因 3'-UTR 中的 rs2070120 相关。这项研究为在 AML 和 ALL 患者中进行 HSCT 时选择更好的候选供体提供了新的见解。
