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

Leuk Lymphoma. 2020 Dec;61(12):2799-2810. doi: 10.1080/10428194.2020.1791851. Epub 2020 Jul 15.


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: B-cells; CD74; CLL; MIF; TCL1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation
  • Leukemia, Lymphocytic, Chronic, B-Cell* / genetics
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics


  • Proto-Oncogene Proteins
  • Tcl1 protein, mouse