TY - JOUR
T1 - Donor heme oxygenase-1 promoter gene polymorphism predicts survival after unrelated bone marrow transplantation for high-risk patients
AU - Horio, Tomohiro
AU - Morishita, Eriko
AU - Mizuno, Shohei
AU - Uchino, Kaori
AU - Hanamura, Ichiro
AU - Espinoza, J. Luis
AU - Morishima, Yasuo
AU - Kodera, Yoshihisa
AU - Onizuka, Makoto
AU - Kashiwase, Koichi
AU - Fukuda, Takahiro
AU - Doki, Noriko
AU - Miyamura, Koichi
AU - Mori, Takehiko
AU - Nakao, Shinji
AU - Takami, Akiyoshi
PY - 2020/2
Y1 - 2020/2
N2 - Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.
AB - Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.
KW - Bone marrow transplantation
KW - HO-1
KW - Single nucleotide polymorphism
KW - Unrelated donor
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U2 - 10.3390/cancers12020424
DO - 10.3390/cancers12020424
M3 - Article
AN - SCOPUS:85079532428
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 424
ER -