Notch signaling pathway and multiple myeloma / 中国实验血液学杂志

ABSTRACT

Notch signaling pathway is a main pathway through cell-cell interactions, which regulates the programmed cell death, cellular proliferation and differentiation in multiple cell systems, and also is an important signaling pathway to modulate the balance between proliferation and differentiation in hematopoietic environment, and is related with the incidence of multiple hematologic malignancies. Multiple myeloma (MM) is malignant in B cell lineage and characterized by clonal proliferative plasma cells. It is very difficult to cure MM patients with a low proliferation rate of the MM cell and drug resistance to the standard dosage of chemotherapy. In recent years, research has shown that in the malignant plasma cells of the patients with multiple myeloma (MM) and the cell lines, but not in normal plasma cells or tumor cells from patients with other malignancies, the Notch ligand Jagged2 was found to be overexpressed. Jagged2 can induce stromal cells to secrete IL-6, VEGF and IGF-1. Notch activation can interact with NF-kappaB and C-myc to promote the proliferation and to inhibit the apoptosis of MM cells, showing in the relationship between the incidence of myeloma and drug resistance. Inhibition of the Notch signaling pathway may induce the apoptosis of MM cells and enhance the effect of chemotherapy. Study indicated that the specific inhibition of Notch signaling by treatment with a gamma-secretase inhibitor (GSI) alone, a specific pharmacologic inhibitor of Notch signaling, induces the apoptosis of myeloma cells and improves sensitivity of myeloma cell to chemotherapy when combined. In this article the composition of Notch signalling pathway, the mechanism of Notch signalling pathway and the relation of Notch signalling pathway to multiple myeloma were reviewed.