CTLA-4 polymorphisms and haplotype correlate with survival in ALL after   allogeneic stem cell transplantation from related   HLA-haplotype-mismatched donor

doi:10.1186/s12967-016-0864-2

CORC > 北京大学 > 生命科学学院

	CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor
	Qin, X.Y. ; Wang, Y. ; Li, G.X. ; Qin, Y.Z. ; Wang, F.R. ; Xu, L.P. ; Chen, H. ; Han, W. ; Wang, J.Z. ; Zhang, X.H. ; Chang, Y.J. ; Liu, K.Y. ; Jiang, Z.F. ; Huang, X.J.
刊名	JOURNAL OF TRANSLATIONAL MEDICINE
	2016
关键词	Allogeneic stem cell transplantation Haplotype CTLA-4 polymorphisms Overall survival ALL SYSTEMIC-LUPUS-ERYTHEMATOSUS BONE-MARROW-TRANSPLANTATION IDENTICAL SIBLING DONORS ACUTE-LEUKEMIA GENE POLYMORPHISMS HEMATOPOIETIC SCT PROMOTER REGION SOLUBLE CTLA-4 T-CELLS ASSOCIATION
DOI	10.1186/s12967-016-0864-2
英文摘要	Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. Methods: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype-mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. Results: ALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111-0.842, P = 0.022).23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA. Conclusion: In summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.; Key Program of National Natural Science Foundation of China [81230013]; National Natural Science Foundation of China [81170483, 81400143]; Beijing Municipal Science and Technology Commission [Z121107002612035]; Scientific Research Foundation for Capital Medicine Development [2011-4022-08]; China National Science and Technology Major Project during 12th Five-Year Plan Period [2012ZX09303019]; SCI(E); PubMed; ARTICLE; huangxiaojun@bjmu.edu.cn; 100; 14
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/433951]
专题	生命科学学院
推荐引用方式 GB/T 7714	Qin, X.Y.,Wang, Y.,Li, G.X.,et al. CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2016.
APA	Qin, X.Y..,Wang, Y..,Li, G.X..,Qin, Y.Z..,Wang, F.R..,...&Huang, X.J..(2016).CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor.JOURNAL OF TRANSLATIONAL MEDICINE.
MLA	Qin, X.Y.,et al."CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor".JOURNAL OF TRANSLATIONAL MEDICINE (2016).