Identification of CD99 as a novel contributor to chronic lymphocytic leukemia progression

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of malignant B cells –a type of white blood cell- in lymphoid tissues and blood. Retention in these tissues provides survival and proliferation signals, therefore contributing to CLL progression. Matrix metalloproteinase-9 (MMP-9) is one of the molecules that controls CLL cell migration and organ retention.

In a work published in Oncogene, the group of Prof. Mª Angeles Garcia Pardo at the Centro de Investigaciones Biológicas (CSIC), in collaboration with the group of Prof. Opdenakker (Rega Institute, Leuven, Belgium) and Dr. García-Marco (Hospital Puerta de Hierro, Madrid), has recently demonstrated that MMP-9 regulates gene and protein expression in CLL, and has identified CD99 as a MMP-9 target.

By performing functional studies, the authors have shown that CD99 is involved in CLL cell adhesion and migration and that reducing CD99 expression inhibits cell migration. Mechanistic analyses indicated that MMP-9 downregulated CD99 via binding to α4ß1 integrin and subsequent inactivation of the Sp1 transcription factor. Comparison of CLL cells from blood and bone marrow of the same individuals demonstrated that the MMP-9-induced mechanism is active in CLL lymphoid tissues.

The study establishes novel functions for MMP-9 and CD99 in CLL progression and supports the role of these molecules as therapeutic targets in this malignancy.

Reference: MMP-9 affects gene expression in chronic lymphocytic leukemia revealing CD99 as an MMP-9 target and a novel partner in malignant cell migration/arrest. Noemí Aguilera-Montilla N, Elvira Bailón, Rebeca Uceda-Castro, Estefanía Ugarte-Berzal, Andrea Santos, Alejandra Gutiérrez-González, Cristina Pérez-Sánchez, Philippe E. Van den Steen, Ghislain Opdenakker, José A. García-Marco and Angeles García-Pardo (2019) Oncogene https://doi.org/10.1038/s41388-019-0744-3