CD74 is dispensable for development of chronic lymphocytic leukemia in Eµ-TCL1 transgenic mice

Abstract

CD74 is a surface protein expressed on immune cells, which acts as receptor for the chemokine macrophage migration inhibitory factor (MIF). Signaling via the 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 Eμ-TCL1 transgenic mice, occurrence of the leukemic phenotype was associated with increased surface CD74 expression. Eμ-TCL1^+/+Cd74^−/− mice showed similar kinetics and clinical features of CLL development as Eμ-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 Eμ-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.

Keywords:

• CD74
• MIF
• TCL1
• CLL
• B-cells

Acknowledgements

The authors thank C. Croce (OSUMC, Ohio, USA) for providing the Eμ-TCL1 mice, R. Bucala (Yale, CT, USA) for the Cd74^−/− mice, and J. Bernhagen (RWTH Aachen, Germany) for recombinant human MIF.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

RB performed research, analyzed the data and wrote the paper; OF performed research and analyzed the data; TV, NRe, P-HN, NRo performed research; AF performed immunohistochemistry staining; MHe designed research study; MHa wrote the Paper; GFR designed the research study, supervised the work and wrote the paper.

Additional information

Funding

This work was supported by grants of the German Cancer Aid [DKH 109158] to GFR, MiHa and MaHe, the German Research Council (DFG) [KFO 286] to MiHa and MaHe, and by the Jose Carreras Leukemia Foundation (DJCLS) [grant number R15/17] to MiHa.