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Published on: July 20, 2016
CXCR4 blockade improves leukemia eradication by allogeneic lymphocyte infusion
Chun-Hui Jin1,2, Yang Li1,2, Jinxing Xia2
1The First Hospital, Institute of Immunology and International Center of Future Science of Jilin University, Changchun, China.
Persistent leukemia in bone marrow causes relapse after stem cell transplants. A CXCR4 antagonist (AMD3100) helps immune cells target leukemia in bone marrow, improving remission rates.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Persistent low-level leukemia in the bone marrow, an immunoprivileged site, is a primary cause of relapse after allogeneic hematopoietic cell transplantation.
- Allogeneic lymphocyte infusion (ALI) is a form of immunotherapy aimed at eradicating residual leukemia cells.
Purpose of the Study:
- To investigate the mechanisms by which leukemia cells evade immune surveillance in the bone marrow.
- To evaluate the efficacy of dislodging leukemia cells from the bone marrow microenvironment to enhance graft-vs.-leukemia effects.
Main Methods:
- Utilized mouse models engrafted with human acute lymphoblastic leukemia derived from MLL-AF9-overexpressing hematopoietic stem cells.
- Administered allogeneic lymphocyte infusion (ALI) with or without the CXCR4 antagonist AMD3100.
- Assessed leukemia burden and remission rates via adoptive transfer experiments and complete remission rate analysis.
Main Results:
- Allogeneic lymphocyte infusion (ALI) selectively spared leukemia cells residing within the bone marrow.
- Treatment with AMD3100 dislodged leukemia cells from the bone marrow, significantly increasing complete remission rates following ALI.
- Combined ALI and AMD3100 treatment markedly reduced the frequency of leukemia-initiating cells in the bone marrow.
Conclusions:
- The immunosuppressive bone marrow microenvironment contributes significantly to leukemia relapse post-immunotherapy.
- Targeting the CXCR4 receptor with AMD3100 can overcome bone marrow-mediated immune resistance.
- AMD3100 may represent a viable clinical strategy to enhance the effectiveness of adoptive allogeneic cell therapy for leukemia.
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