Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates <40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.
|State||Published - Dec 1 2019|
Bibliographical noteFunding Information:
The authors thank Drs. Alex Sparreboom and Navjot Pabla for helpful discussions and insights and Dr. Adrianne M. Dorrance for providing critical reagents. This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children’s Research Hospital, OSU Comprehensive Cancer Center Pelotonia Funds, National Institutes of Health Cancer Center Support Grant P30 CA021765 (SJCRH), P30 CA016058 (OSUCCC), R01 CA138744 (S.D.B.), and F32 CA180513 (C.D.D.).
© 2019, The Author(s).
ASJC Scopus subject areas
- Chemistry (all)
- Biochemistry, Genetics and Molecular Biology (all)
- Physics and Astronomy (all)