Mechanisms of Graft-vs. -Leukemia Against a Novel Murine Model of Chronic Myelogenous Leukemia
Annual rept. 1 Jul 2003-30 Jun 2004
YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
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Our objective is to understand the immunobiology underlying the differential sensitivity of chronic phase and blast crisis CML. Our data thus far support the hypothesis that GVL against mCP-CML can be mediated by redundant processes, and that impairment of an individual pathway is insufficient to prevent GVL. We hypothesize that GVL against BC-CML is less forgiving than that against CP-CML, and that multiple effector pathways must act in concert for effective GVL. In the last year we have created BC-CML in B6 mice and have established the basic features of the model 1 survival versus cell dose 2 that GVL requires alloantigen differences 3 that GVL can be mediated by unfractionated lymph node cells 4 that GVL can be mediated by purified CD4 or CD8 cells, but that large doses are required. We are currently creating gene-deficient BC-CML and anticipate rapid progress this year in identifying key effector mechanisms and modes of antigen presentation.
- Medicine and Medical Research