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Publication : IFN-γ promotes graft-versus-leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic cell transplantation.

First Author  Yang Y Year  2011
Journal  Blood Volume  118
Issue  13 Pages  3721-4
PubMed ID  21835954 Mgi Jnum  J:177056
Mgi Id  MGI:5293558 Doi  10.1182/blood-2010-05-283887
Citation  Yang Y, et al. (2011) IFN-{gamma} promotes graft-versus-leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic cell transplantation. Blood 118(13):3721-4
abstractText  The ability of IFN-gamma to enhance graft-versus-leukemia (GVL) activity without direct interaction with leukemia cells was examined by comparing GVL effects against IFN-gamma receptor-deficient (GRKO) leukemia between wild-type (WT) and IFN-gamma-deficient (GKO) allogeneic hematopoietic cell transplantation (allo-HCT). We established a primary IFN-gamma-unresponsive T-cell leukemia model using virally-transduced GRKO B6 mouse bone marrow cells overexpressing Notch1. We first assessed GVL effects in lethally-irradiated B6 mice receiving CD4-depleted allo-HCT from WT or GKO BALB/c donors. Administration of CD4(+) cell-depleted allo-HCT from WT, but not GKO, BALB/c donors mediated significant GVL effects against GRKO leukemia. Similar results were obtained in pre-established allogeneic chimeras receiving delayed donor lymphocyte infusion (DLI). Although both WT and GKO DLI achieved significant anti-tumor responses, the former was markedly stronger than the latter. These data indicate that IFN-gamma is capable of promoting GVL effects via mechanisms independent of its interaction with leukemia cells.
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