Search for immunoregulatory microRNAs based on genetic polymorphism function related to hematopoietic cell transplantation View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2018-2022

FUNDING AMOUNT

4420000.0 JPY

ABSTRACT

By the previous year, multiple Toll-like receptor (TLR) -related polymorphic genes were found to be associated with post-allogeneic transplant outcomes. Therefore, we focused on the UNC-93B1 gene polymorphism rs308328 (T> C) that integrates TLR function, and 237 cases of blood cancer (115 cases of acute myelogenous leukemia, 115 cases of acute lymphocytic leukemia) who underwent allogeneic bone marrow transplantation between unrelated persons. UNC-93B1 gene polymorphism and post-transplant outcome in 46 cases, myeloplastic syndrome 38 cases, malignant lymphoma 24 cases, chronic myelogenous leukemia 10 cases, myeloproliferative tumor 3 cases, multiple myeloproliferative tumor 1 case) We examined the relationship with (Genes Immun 2021). Transplantation from UNC93B1 C / C type (= low inducible type) donors has a significantly higher disease-free survival rate (77% vs. 58) than UNC93B1 C / T or T / T type (= high inducible type) donors. %; p <0.01), and there was a tendency for less infectious disease deaths. This indicates that TLR-based hyperresponsiveness may be associated with fatal complications after transplantation, and is expected to lead to the development of new therapies in the future. Furthermore, vascular endothelial cell-related gene polymorphisms, especially ADAMTS13 rs2285489, were found to be associated with suppression of acute leukemia recurrence after allogeneic hematopoietic stem cell transplantation (Int J Mol Sci 2019), and functional analysis was undertaken. Prevention and treatment of recurrence after allogeneic transplantation is the greatest unmet need for allogeneic transplantation and is considered important. Although the prognosis of leukemia / allogeneic transplant patients with low blood ADAMTS13 concentration is considered to be poor, the addition of recombinant ADAMTS13 in vitro did not increase the alloimmunity effect or anticancer drug effect on leukemia (not yet). Announcement data). Considering that the ADAMTS13 gene polymorphism itself or the molecules and signaling pathways of vascular endothelial cells involved in ADAMTS13 expression are involved in the induction of anti-leukemia effect, we plan to establish an ADAMTS13 gene polymorphism-modified human vascular endothelial cell clone by genome editing. ing. More... »

URL

https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K08343

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