Title : The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia.

Pub. Date : 2015 Jan

PMID : 24912431






5 Functional Relationships(s)
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1 The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom"s Macroglobulinemia. ibrutinib C-X-C motif chemokine receptor 4 Homo sapiens
2 CXCR4(WHIM) somatic mutations are common Waldenstrom"s Macroglobulinemia (WM), and are associated with clinical resistance to ibrutinib. ibrutinib C-X-C motif chemokine receptor 4 Homo sapiens
3 SDF-1a-treated CXCR4(S338X) WM cells showed sustained AKT and ERK activation and decreased apoptotic changes versus CXCR4(WT) cells following ibrutinib treatment, findings which were also reversed by AMD3100. ibrutinib C-X-C motif chemokine receptor 4 Homo sapiens
4 AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance. ibrutinib C-X-C motif chemokine receptor 4 Homo sapiens
5 AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance. ibrutinib C-X-C motif chemokine receptor 4 Homo sapiens