Inhibition of the JAK-STAT3-Mcl-1 Axis by Combining Ruxolitinib with S63845 Completely Prevents Plasmacytoma Growth in the Gp130-Regulated INA-6 Xenograft Mouse Model

Growth of malignant plasma cells in multiple myeloma is regulated by the JAK/STAT3 pathway via cytokines such as interleukin(IL)-6 which is produced in the bone marrow microenvironment. IL-6 stimulation leads to upregulation of anti-apoptotic proteins of the Bcl-2 family including Mcl-1 and/or Bcl-xL. Growth of INA-6 plasmacytomas in SCID mice depends on activation of the signal transducer gp130, the common receptor for IL-6 and other cytokines of the IL-6/gp130 family (Burger et al., Haematologica 102, 2017).
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research