MYD88 Inhibitor ST2825 Suppresses the Growth of Lymphoma and Leukaemia Cells

Background/aim: Myeloid differentiation primary response gene 88 (MyD88), which activates the nuclear factor kappa B (NF-κB) pathway, is important for the growth of lymphoma and leukaemia cells. In this study, we investigated the effects of ST2825, a synthetic peptidomimetic compound which inhibits MyD88 homodimerization, on their growth.

Materials and methods: Seven lymphoma and leukaemia cell lines including TMD8, a B-cell lymphoma line with MYD88-activating mutation, were treated with ST2825 and analysed for cell proliferation and expression of NF-κB signalling-related molecules.

Results: ST2825 suppressed the growth of all cell lines by inducing Apoptosis and down-regulating phosphorylation of NF-κB pathway components inhibitor of nuclear factor kappa B kinase (IκB) and reticuloendotheliosis oncogene A (RelA), as well as of MyD88 activator Bruton tyrosine kinase (Btk), suggesting that MyD88 may affect Btk activity. ST2825 effects were specific as MYD88-targeting siRNA also suppressed phosphorylation of NF-κB signalling proteins and Btk in TMD8 cells.

Conclusion: ST2825 may be a novel drug targeting not only B-lymphoid malignancies with MyD88 mutations, but also lymphoma and leukaemia with wild-type MyD88.