Association between single nucleotide polymorphisms within HLA region and disease relapse for patients with hematopoietic stem cell transplantation

• Published in: Scientific reports Vol. 9; no. 1; pp. 13731 - 8
• Main Authors: Chen, Ding-Ping, Chang, Su-Wei, Wang, Po-Nan, Hus, Fang-Ping, Tseng, Ching-Ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.09.2019; Nature Publishing Group
• Subjects: 45/23; 45/77; 692/308/2056; 692/4017; Acute myeloid leukemia; Adolescent; Adult; Base pairs; Child; Child, Preschool; DOA gene; Donors; Female; Graft vs Host Disease - genetics; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histocompatibility antigen HLA; HLA Antigens - genetics; Humanities and Social Sciences; Humans; Leukemia; Leukemia, Myeloid, Acute - genetics; Lymphatic leukemia; Lymphotoxin; Male; Middle Aged; multidisciplinary; Myeloid leukemia; Notch4 protein; Polymorphism, Single Nucleotide - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Promoter Regions, Genetic - genetics; Recurrence; RING1 gene; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Stem cell transplantation; Stem cells; Transplantation; Transplantation, Homologous - methods; Young Adult
• ISSN: 2045-2322; 2045-2322
• 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.