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

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

Fingerprint

Chemotherapy
RNA Interference
RNA
Acute Myeloid Leukemia
Bone Marrow Cells
Bone
Cells
Drug Therapy
Recombinant Fusion Proteins
Transplants
Arginine
Heme Oxygenase-1
Daunorubicin
Stem cells
Antibodies
Small Interfering RNA
Myeloid Leukemia
Blood
Fusion reactions
Therapeutics

Keywords

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

Cite this

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title = "CD64-targeted HO-1 RNA interference enhances chemosensitivity in orthotopic model of acute myeloid leukemia and patient-derived bone marrow cells",
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.",
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year = "2020",
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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. / Yong, Seok Beom; Chung, Jee Young; Kim, Seong Su; Choi, Hyung Seok; Kim, Yong Hee.

In: Biomaterials, Vol. 230, 119651, 02.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CD64-targeted HO-1 RNA interference enhances chemosensitivity in orthotopic model of acute myeloid leukemia and patient-derived bone marrow cells

AU - Yong, Seok Beom

AU - Chung, Jee Young

AU - Kim, Seong Su

AU - Choi, Hyung Seok

AU - Kim, Yong Hee

PY - 2020/2

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N2 - 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.

AB - 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.

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