IL-8 secreted in a macrophage migration-inhibitory factor-and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival

I Binsky, M Haran, D Starlets, Y Gore… - Proceedings of the …, 2007 - National Acad Sciences
I Binsky, M Haran, D Starlets, Y Gore, F Lantner, N Harpaz, L Leng, DM Goldenberg…
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
Chronic lymphocytic leukemia (CLL) is a malignant disease of small mature lymphocytes.
Previous studies have shown that CLL B lymphocytes express relatively large amounts of
CD74 mRNA relative to normal B cells. In the present study, we analyzed the molecular
mechanism regulated by CD74 in B-CLL cells. The results presented here show that
activation of cell-surface CD74, expressed at high levels from an early stage of the disease
by its natural ligand, macrophage migration-inhibition factor (MIF), initiates a signaling …
Chronic lymphocytic leukemia (CLL) is a malignant disease of small mature lymphocytes. Previous studies have shown that CLL B lymphocytes express relatively large amounts of CD74 mRNA relative to normal B cells. In the present study, we analyzed the molecular mechanism regulated by CD74 in B-CLL cells. The results presented here show that activation of cell-surface CD74, expressed at high levels from an early stage of the disease by its natural ligand, macrophage migration-inhibition factor (MIF), initiates a signaling cascade that contributes to tumor progression. This pathway induces NF-κB activation, resulting in the secretion of IL-8 which, in turn, promotes cell survival. Inhibition of this pathway leads to decreased cell survival. These findings could form the basis of unique therapeutic strategies aimed at blocking the CD74-induced, IL-8- dependent survival pathway.
National Acad Sciences