Simon Mitchell @mitchell.science · Dec 6 Imaging confirms it! Chronic NF-kB activation creates crosstalk between the pathways. We also knew this chronic NF-kB was causing the drug resistance, because when we inhibit it (with ibrutinib) we can re-sensitize the cells. But the link between cRel and MCL1 is new. Is it real?
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ChIPseq says yes, but we needed another test. The model told us an IkBe knockout would selectively upregulate cRel, which would upregulate MCL1 if we were right. Collaborating with Alexander Hoffmann's group we tested this in IkBe KO mice. cRel and MCL1 go up!