Cd74 Is Dispensable For Development Of Chronic Lymphocytic Leukemia Ine Mu-Tcl1 Transgenic Mice

CD74 is a surface protein expressed on immune cells, which acts as receptor for the chemokine macrophage migration inhibitory factor (MIF). Signalingviathe MIF/CD74-axis has been reported to be important for the pathogenesis of chronic lymphocytic leukemia (CLL). We wanted to clarify the role of CD74 in MIF-induced signaling/leukemic development. In E mu-TCL1 transgenic mice, occurrence of the leukemic phenotype was associated with increased surface CD74 expression. E mu-TCL1(+/+)Cd74(-/-)mice showed similar kinetics and clinical features of CLL development as E mu-TCL1(+/+)mice. MIF stimulation of leukemic splenocytes led to AKT activation in a CD74-dependent manner. AKT activation was reduced in Cd74-deficient splenocytes in the presence of the oncogenic TCL1-transgene. Tumor cell apoptosis/proliferation were unaffected in E mu-TCL1(+/+)Cd74(-/-)mice. Our data suggest that the need for active CD74 signaling is overcome in the leukemic context of TCL1-driven CLL, and that CD74 may have a dispensable role for CLL pathogenesis in this model.