Development of novel molecular-targeting therapy for multiple myeloma against its progenitor cells

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Multiple myeloma is a refractory hematological malignancy to cure, and it will be desired new therapeutic approaches. Based on the recent progress of the stem cell biology, it has been considered to develop the new therapy against the myeloma stem/progenitor cells(MSPC) to cure the patients. In the present project, I developed new NF-kB inhibitor, TM233, from natural compound 1'-acetoxychavicol acetate(ACA), which has more potent NF-kB inhibition activity than that of ACA and induces apoptosis of myeloma cells. In addition, TM233 induced apoptosis of proteasome inhibitor bortezomib-resistant myeloma cells ; therefore TM233 will expected to be future clinical application. Gold compound, auranofin, also induced apoptosis of myeloma cells via inhibition of JAK/STAT and NF-kB signaling pathways. It has been cleared that clonogenic MSPC is existed in CD138-negative plasma cell fraction in vitro and in vivo. Further studies will be needed to investigate the effect of TM233, auranofin and other natural compounds on MSPC.