Erika Shiratori1, Mai Itoh1, Shuji Tohda2. 1. Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 2. Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan tohda.mlab@tmd.ac.jp.
Abstract
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. Copyright
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. Copyright
Authors: Emma Muiños Lopez; Kevin Leclerc; Malissa Ramsukh; Paulo El Parente; Karan Patel; Carlos J Aranda; Anna M Josephson; Lindsey H Remark; David J Kirby; Daniel B Buchalter; Tarik Hadi; Sophie M Morgani; Bhama Ramkhelawon; Philipp Leucht Journal: Bone Date: 2022-01-06 Impact factor: 4.626
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