Role of CD74 in Mesenchymal Stem Cell Dysfunction in Patients with Acute Myeloid Leukemia

Abstract 4344

Mesenchymal stem cell (MSC) dysfunction has been implicated in the biology of the acute myeloid leukemia (AML). Preliminary studies from our laboratory have demonstrated that MSCs derived from AML patients have diminished T cell immunosuppressive capacity, and these MSCs demonstrate signs of transformation. In the current study, we seek to explore the mechanisms of MSC dysfunction in patients with AML. Recent reports have implicated migration inhibitory factor (MIF) and its receptor CD74 in cancer progression. CD74 is a cell surface glycoprotein that also serves as the invariant chain for the class II major histocompatibility complex (MHC-II). The significance of these studies is two-fold: (1) CD74 participates in intracellular signal transduction via NF-kappaB, ERK, and PI(3)K pathways, thereby promoting cell proliferation, and (2) MHC-II invariant chain expression in MSCs may prevent tumor antigen loading and presentation to T cells, allowing for immune subversion. Our results show increased expression of CD74 on MSCs derived from AML patients. The readily targetable phenotype and the availability of anti-CD74 antibody milatuzumab merits further investigation into the role of CD74 in AML biology.