Recipient ADAMTS13 Single-Nucleotide Polymorphism Predicts Relapse after Unrelated Bone Marrow Transplantation for Hematologic Malignancy

Nomoto, Haruka; Takami, Akiyoshi; Espinoza, J. Luis; Onizuka, Makoto; Kashiwase, Koichi; Morishima, Yasuo; Fukuda, Takahiro; Kodera, Yoshihisa; Doki, Noriko; Miyamura, Koichi; Mori, Takehiko; Nakao, Shinji; Morishita, Eriko

doi:10.3390/ijms20010214

Cited by 5 publications

(5 citation statements)

References 29 publications

(36 reference statements)

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“…Lasparaginase is known to alter many coagulation and anticoagulant proteins, whereas ALL patients are often treated with L-asparaginase in chemotherapy [18,19], and L-asparaginase may be a potential cause of ADAMTS-13 activity, which is worth researching in detail in the future. Lower translational activity associated with the ADAMTS-13 rs2285489 C/C genotype in hepatic stellate cells might contribute to an increased incidence of relapse [20], which suggests that ADAMTS-13 Fig. 2 The survival curve started from the day of onset, followed for 24 months since the day the leukemia was onset.…”

Section: Discussionmentioning

confidence: 99%

Decreased activity of plasma ADAMTS-13 predicts poor prognosis in acute lymphoblastic leukemia patients after hematopoietic stem cell transplant

Chen

et al. 2020

J Hematopathol

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Decreased ADAMTS-13 is important for the diagnosis of thrombotic thrombocytopenic purpura (TTP), but recent studies have shown that reduced ADAMTS-13 activity is associated with disease prognosis of a variety of cancer patients. As an important hematological malignancy, the significance of ADAMTS-13 in acute lymphoblastic leukemia (ALL) has not been fully elucidated. This research aims to explore the significance of decreased ADAMTS-13 activity in acute lymphoblastic leukemia after hematopoietic stem cell transplant (HSCT). Thirty-eight ALL patients were included in this research, and their ADAMTS-13 activity was measured before HSCT, including 21 patients with low ADAMTS-13 activity (< 481 ng/ml) and 17 patients with normal ADAMTS-13 activity (481-785 ng/ml). Related medical indicators before HSCT and 1 month after HSCT were collected. All the patients were followed and their progress was recorded and evaluated. Level changes of related medical indicators and prognosis situations were compared between two groups. ALL patients with low ADAMTS-13 activity suffered more HSCTrelated complications than patients with normal ADAMTS-13 activity. There was no significant difference for APTT, PT, CRP, and D-dimer between two groups. Low ADAMTS-13 Group underwent higher mortality rate than Normal Group during the 1year follow-up after HSCT and 2-year follow-up after the onset of ALL. To conclude, low ADAMTS-13 activity predicts poor prognosis of ALL after HSCT.

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Section: Discussionmentioning

confidence: 99%

Decreased activity of plasma ADAMTS-13 predicts poor prognosis in acute lymphoblastic leukemia patients after hematopoietic stem cell transplant

Chen

et al. 2020

J Hematopathol

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“…The HO-1 rs2071746 SNP was analyzed in 593 HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 allele-matched, unrelated BMT donor-transplant recipient pairs (Table 1). Based on the disease status and other risk factors that influence post-transplant outcomes, as previously reported [22,[27][28][29], standard-risk disease was defined as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or multiple myeloma (MM) in the first complete remission; malignant lymphoma (ML) in any complete remission; or myelodysplastic syndrome (MDS) or chronic myeloid leukemia (CML) in the chronic phase. Both ALL and AML, which were in the second complete remission, were included in the high-risk group, according to recent reports [27,29] indicating that patients with AML and ALL in the second complete remission have worse post-transplant outcomes than those in the first complete remission.…”

Section: The Frequencies Of Ho-1 Genotypesmentioning

confidence: 99%

“…One important single nucleotide polymorphism (SNP) in the promoter region of the HO-1 gene, rs2071746 (-413A>T), is functional, and the major A allele is reported to be associated with higher expression of HO-1 than the minor T allele [18,19]. There is growing evidence to support that non-human leukocyte antigen (HLA) genetic polymorphism represents a significant determinant of outcomes after allo-HSCT [20][21][22][23][24][25][26]. These findings prompted us to investigate the impact of the rs2071746 SNP in the HO-1 gene on the clinical outcomes of patients undergoing allogeneic bone marrow transplantation (BMT), using an HLA allele-matched, unrelated donor through the Japan Marrow Donor Program (JMDP).…”

Section: Introductionmentioning

confidence: 99%

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Horio

Morishita

Mizuno

et al. 2020

Cancers

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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.

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“…However, lifethreatening complications associated with allogeneic SCT, such as severe infection, organ damage, and graft-versushost disease (GVHD), remain obstacles to overcome [1]. Recently, increasing evidence has suggested that non-HLA genetic polymorphisms significantly influence outcomes after allogeneic SCT [2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

et al. 2021

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UNC-93 homolog B1 (UNC93B1) is a key regulator of toll-like receptors (TLRs), pattern recognition receptors that sense invading pathogens and manage the innate immune response and deliver them from the endoplasmic reticulum to their respective endosomal signaling compartments. Several types of TLRs are known to contribute to the inflammatory process after allogeneic hematopoietic stem cell transplantation (SCT), so UNC93B1 might play integral roles there. We investigated the influence of the UNC93B1 single-nucleotide polymorphism (SNP) rs308328 (T>C) on transplant outcomes in a cohort of 237 patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The donor UNC93B1 C/C genotype was associated with a better 3-year overall survival than the donor UNC93B1 C/T or T/T genotype. An analysis of the UNC93B1 rs308328 genotype may therefore be useful for selecting the donor, estimating the prognosis, and creating therapeutic strategies after allogeneic SCT.

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Recipient ADAMTS13 Single-Nucleotide Polymorphism Predicts Relapse after Unrelated Bone Marrow Transplantation for Hematologic Malignancy

Cited by 5 publications

References 29 publications

Decreased activity of plasma ADAMTS-13 predicts poor prognosis in acute lymphoblastic leukemia patients after hematopoietic stem cell transplant

Decreased activity of plasma ADAMTS-13 predicts poor prognosis in acute lymphoblastic leukemia patients after hematopoietic stem cell transplant

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

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