Preventing chemotherapy-induced myelosuppression by repurposing the FLT3 inhibitor quizartinib

Samuel Taylor, Johanna Duyvestyn, Samantha Zeps, Emma Dishington, Catherine Rinaldi, Oliver M. Dovey, George Vassiliou, Carolyn Grove, Wallace Langdon

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Here we describe an approach to inhibit chemotherapy-induced myelosuppression. We found that short-term exposure of mice to the FLT3 inhibitor quizartinib induced the transient quiescence of multipotent progenitors (MPPs). This property of quizartinib conferred marked protection to MPPs in mice receiving fluorouracil or gemcitabine. The protection resulted in the rapid recovery of bone marrow and blood cellularity, thus preventing otherwise lethal myelosuppression. A treatment strategy involving quizartinib priming that protected wild type bone marrow progenitors, but not leukemic cells, from fluorouracil provided a more effective treatment than conventional induction therapy in mouse models of acute myeloid leukemia. This strategy has the potential to be extended for use in other cancers where FLT3 inhibition does not adversely affect the effectiveness of chemotherapy. Thus, the addition of quizartinib to cancer treatment regimens could markedly improve cancer patient survival and quality of life.
Original languageEnglish
Article numberaam8060
Number of pages14
JournalScience Translational Medicine
Volume9
Issue number402
DOIs
Publication statusPublished - 9 Aug 2017

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