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FOXP3 polymorphism increases risk of hepatic veno-occlusive disease and CMV infection after allogeneic hematopoietic stem cell transplantation in pediatric acute leukemia patients
소아 급성 백혈병 환자에서 FOXP3 유전자 다형성과 동종 조혈모세포 이식 후 간정맥폐색성질환과 사이토메갈로바이러스감염의 위험성

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Authors
박철
Advisor
신희영
Major
의과대학 협동과정 종양생물학전공
Issue Date
2016-02
Publisher
서울대학교 대학원
Keywords
FOXP3rs3761548hematopoietic stem cell
Description
학위논문 (박사)-- 서울대학교 대학원 : 의과대학협동과정 종양생물학전공, 2016. 2. 신희영.
Abstract
Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapeutic option for high-risk acute leukemia, but it can cause severe complications. Homeostasis of immune function plays a key role in the development of some of these complications, and regulatory T cells (Tregs) are known to have an important role in maintaining the immune homeostasis.
i
Expression of Forkhead BOX P3 (FOXP3) is essential for the development of Tregs. The main aim of this study was to evaluate the potential influence of FOXP3 rs3761548 polymorphisms of donor on the outcomes of the HSCT.
Methods: A total of 171 patients were enrolled in this study and genotyping was done with PCR and direct sequencing using the post-transplant samples, which showed the complete replacement of hematopoietic cells by donor. We grouped the patients according to the genotype and compared the clinical outcomes using the Log- rank test and Gray test.
Results: The patients who received HSCT from the donor with rs3761548 CC genotype had higher incidence of hepatic veno- occlusive disease (HVOD) and cytomegalovirus (CMV) infection compared to those of AA or AC genotype group (24.9% vs. 8.5%, P=0.011 and 66.3% vs. 47.6%, P=0.023). Treatment-related mortality (TRM) rate of patients with AA or AC genotype was lower than that of the other patients with CC genotype (3.4% vs. 14.2%, P=0.044) resulting in the difference of overall survival. There was no difference in graft-versus-host disease (GVHD), relapse or blood stream infection (BSI) according to the rs3761548 ii
genotype. In multivariate analysis, CC genotype maintained its statistical significance in the development of HVOD (HR=3.97, 95% CI=1.47-10.74) and CMV infection (HR=1.88, 95% CI=1.19- 2.97), showing lower overall survival.
Conclusions: This is the first report on FOXP3 rs3761548 SNP in allogeneic HSCT and this SNP can be considered as a candidate marker for predicting the development of HVOD and CMV infection after allogeneic HSCT.
Language
English
URI
https://hdl.handle.net/10371/121779
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Theses (Ph.D. / Sc.D._협동과정-종양생물학전공)
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