Abstract 907: Efficacy of SAR302503, a JAK2 inhibitor, in primary human acute myeloid leukemia xenografts

Autor: Andreea C. Popescu, John E. Dick, Cynthia J. Guidos, Yan Xing, Julie Yuan, Mark D. Minden, Donna E. Hogge, Gitte Gerhard, Jean Cy Wang, Weihsu C. Chen
Rok vydání: 2013
Předmět:
Zdroj: Cancer Research. 73:907-907
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2013-907
Popis: Small molecule inhibitors of Janus kinase 2 (JAK2) such as Ruxolitinib and SAR302503 have demonstrated efficacy in clinical trials for treatment of myeloproliferative disorders. Activated JAK2 signaling has been reported in some acute myeloid leukemia (AML) samples even though JAK2 mutations are relatively rare in AML. Whether JAK2 inhibitors are effective in AML, particularly against the disease-sustaining leukemia stem cells (LSC), is not clear. We report that SAR302503 (Sanofi, Cambridge MA), an orally administered small molecule JAK2 inhibitor, shows efficacy in a xenograft model of human AML established by intrafemoral injection of primary AML cells into sublethally irradiated NOD.SCID mice. The AML samples tested were of multiple subtypes with heterogeneous cytogenetic and molecular abnormalities. Starting 2 weeks post transplantation to permit establishment of an AML graft, mice received twice daily oral gavage with 60 mg/kg SAR302503 or vehicle alone (0.5% methylcellulose) for 14 consecutive days. In 17 of 34 AML samples, SAR302503 treatment reduced leukemic engraftment in the injected femur (56-94% relative reduction, RR, compared to controls; p Citation Format: Weihsu C. Chen, Andreea C. Popescu, Yan Xing, Gitte Gerhard, Julie Yuan, Mark Minden, Cynthia Guidos, Donna E. Hogge, John E. Dick, Jean CY Wang. Efficacy of SAR302503, a JAK2 inhibitor, in primary human acute myeloid leukemia xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 907. doi:10.1158/1538-7445.AM2013-907
Databáze: OpenAIRE
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