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

Seok Beom Yong, Jee Young Chung, Seong Su Kim, Hyung Seok Choi, Yong Hee Kim

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish
Article number119651
JournalBiomaterials
Volume230
DOIs
StatePublished - 2020 Feb

Keywords

  • Acute myeloid leukemia
  • CD64-Targeted fusion protein
  • HO-1 silencing-mediated chemo-sensitization
  • Monocytic myeloid leukemia

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