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CD64-targeted HO-1 RNA interference enhances chemosensitivity in orthotopic model of acute myeloid leukemia and patient-derived bone marrow cells

Title
CD64-targeted HO-1 RNA interference enhances chemosensitivity in orthotopic model of acute myeloid leukemia and patient-derived bone marrow cells
Author
김용희
Keywords
Acute myeloid leukemia; Monocytic myeloid leukemia; CD64-Targeted fusion protein; HO-1 silencing-mediated chemo-sensitization
Issue Date
2020-02
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v. 230, article no. 119651
Abstract
Acute myeloid leukemia is the most frequent and life-threatening blood cancer. The main treatment is chemotherapy, sometimes followed by stem cell transplant. Resistance to chemotherapy and hepatotoxicity of the CD33-targeted therapy require an alternative therapeutic strategy. Here, we report CD64-targeted RNA interference as a novel AML therapy, which was delivered by a recombinant fusion protein of CD64-binding antibody and nona-arginine (sR9). The sR9-mediated heme oxygenase-1 siRNA (siHO-1) delivery efficiently enhanced apoptotic response to daunorubicin of AML cells and AML-targeted HO-1 silencing improved chemotherapy and prolonged survival in orthotopic myeloid leukemia model. CD64 expression was verified and HO-1-silencing-mediated chemo-sensitization was also validated in leukemic blast cells originated from AML M4/M5 patient's bone marrow. Collectively, CD64-targeted RNA interference could be a promising strategy for AML therapy and AML-targeted HO-1 suppression is expected to improve the chemotherapeutic effect in future clinical trials.
URI
https://www.sciencedirect.com/science/article/pii/S0142961219307501?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/161557
ISSN
0142-9612; 1878-5905
DOI
10.1016/j.biomaterials.2019.119651
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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