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トピック - 【基礎研究】Hierarchy for targeting pro-survival BCL2 family proteins in multiple myeloma: pivotal role of MCL1.

書誌情報:Gong JN,et al. 2016 Jul 27.  Pubmed

カテゴリー:基礎研究


Abstract:
New therapeutic targets are needed to address the poor prognosis of patients with high-risk multiple myelomaMyeloma cells usually express a range of the pro-survival BCL2 proteins. To define the hierarchy of their relative importance for maintaining the survival ofmyeloma cells, we targeted each of them in a large panel of cell lines using pharmacological inhibitors, gene editing or by peptide-based approaches, alone or in combination. The majority of well-established immortalized cell lines (17/25) or low-passage myelomacell lines (5/7) are readily killed when MCL1 is targeted, even including those cell lines sensitive to BCL2 inhibition. Targeting MCL1also constrained the growth of myeloma in vivo. We also identified a previously unrecognized sub-set of myeloma that is highly BCLXL-dependent, and the potential for co-targeting MCL1 and BCLXL. As MCL1 is pivotal for maintaining survival of most myelomas, it should be prioritized for targeting in the clinic once high quality, validated inhibitors become available.

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