Abstract 795: Isatin analog for the treatment of acute myeloid leukemia

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with therapeutic modalities relying on traditional cytotoxic therapies and hematopoietic stem cell transplantation. Current first-line cytotoxic chemotherapy exhibits limited success, with 50% of younger patients and 80% of older patients succumbing to the disease. There is an urgent unmet need for new therapeutics in acute myeloid leukemia (AML) as standard therapy has not changed in the past three decades and outcome remains poor for most patients. Our group has reported cytotoxic potential of dibromo-derivative of isatin, 5,7-dibromo-N-(p-thiocyanomethylbenzyl)isatin (KS99) against variety of solid tumors and multiple myeloma (MM) cells by inhibiting BTK, AKT and tubulin polymerization. In this study, we examined the ability of KS99, to inhibit the growth of panel of human AML cell lines and primary samples collected from AML patients. After 48h exposure, KS99 inhibited the growth of AML cell lines (IC50, 150-225nM) and primary blast samples (IC50, 600-1300nM) in a dose dependent manner. KS99 treatment also selectively reduced the clonogenicity of human acute myeloid leukemia patient cells compared to the hematopoietic stem cells. We also found that KS99 induced apoptosis by modulating expression of Mcl-1 and Bcl-2. Further studies will aim to determine the mechanism of action of KS99 and as a single agent and in combination with anti-leukemia agents and demonstrate the preclinical efficacy in AML animal models including AML patient derived xenografts. Together, these data demonstrate the therapeutic efficacy of Isatin analog and suggest that KS99 should be further developed as a novel therapeutic agent for AML. Citation Format: Krishne Gowda, Charyguly Annageldiyev, Dhimant Desai, Shantu Amin, David Claxton, Arati Sharma. Isatin analog for the treatment of acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 795.