CXCR4 blockade improves leukemia eradication by allogeneic lymphocyte infusion.

ABSTRACT: Persistent low levels of disease in bone marrow, an immunoprivileged tissue, are responsible for relapse following allogeneic hematopoietic cell transplantation. Using mouse models carrying primary human acute lymphoblast leukemia derived from MLL-AF9-overexpressing human hematopoietic stem cells, we demonstrate that allogeneic lymphocyte infusion (ALI)-mediated graft-vs.-leukemia effects selectively spare leukemia cells in the bone marrow. The resistance of leukemia cells to ALI within bone marrow is due to the immunosuppressive status of the tissue, as ALI achieved a significantly increased complete remission rate when leukemia cells were dislodged from bone marrow by treatment with a CXCR4 antagonist AMD3100. Adoptive transfer experiments confirmed that the frequency of leukemia-initiat

SUBMITTER: Jin CH 

PROVIDER: S-EPMC5992083 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature