Discovery of donor genotype associated with long-term survival of patients with hematopoietic stem cell transplantation in refractory acute myeloid leukemia
- 주제(키워드) Donor genotype , hematopoietic stem cell transplantation , acute myeloid leukemia , whole-exome sequencing , survival
- 주제(기타) Oncology
- 주제(기타) Hematology
- 등재 SCIE, SCOPUS
- 발행기관 TAYLOR & FRANCIS LTD
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000161258
- 본문언어 영어
- Published As http://dx.doi.org/10.1080/10428194.2018.1542142
- PubMed https://pubmed.ncbi.nlm.nih.gov/30507323
초록/요약
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10-20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c.2982C>T and CDH11 c.945G>A. To validate the protective effects of these leukemia-clearing genotypes (LCGs), AML patients who received allo-HSCT in a complete-remission status were also analyzed. Twenty-two of 96 donors (22.9%) had LCGs in their genomes, and overall survival was significantly longer in patients who received allo-HSCT from donors with germ-line LCGs (hazard ratio=0.47, 95% confidence interval=0.24-0.94, p=.033). These findings indicate that donor germ-line LCGs have phenotypically leukemia-clearing effects and are biomarkers for predicting clinical outcomes in allogeneic transplantation in AML patients.
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