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按下贪睡按钮:使用FLT3抑制剂quizartinib诱导静止状态可保护造血祖细胞免受化疗影响。

Hitting the snooze button: Inducing quiescence with the FLT3 inhibitor quizartinib protects hematopoietic progenitors from chemotherapy.

作者信息

Taylor Samuel J, Langdon Wallace Y

机构信息

Department of Pathology and Laboratory Medicine, School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia, Australia.

出版信息

Mol Cell Oncol. 2017 Sep 19;4(6):e1378156. doi: 10.1080/23723556.2017.1378156. eCollection 2017.

DOI:10.1080/23723556.2017.1378156
PMID:29209657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5706937/
Abstract

Myelosuppression is one of the most severe and limiting side effects of chemotherapy. Our recent work outlines a strategy to prevent chemotherapy-induced myelosuppression by administering a priming dose of the FMS-Like Tyrosine kinase 3 (FLT3) inhibitor quizartinib. Furthermore, by administering sequential quizartinib primed injections of fluorouracil (5-FU), we demonstrated a novel and effective strategy to eliminate disease in two mouse models of quizartinib resistant acute myeloid leukemia (AML).

摘要

骨髓抑制是化疗最严重且具有限制性的副作用之一。我们最近的研究概述了一种通过给予初始剂量的FMS样酪氨酸激酶3(FLT3)抑制剂奎扎替尼来预防化疗诱导的骨髓抑制的策略。此外,通过连续给予经奎扎替尼预处理的氟尿嘧啶(5-FU)注射,我们在两种奎扎替尼耐药的急性髓系白血病(AML)小鼠模型中证明了一种消除疾病的新颖且有效的策略。

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2
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本文引用的文献

1
Preventing chemotherapy-induced myelosuppression by repurposing the FLT3 inhibitor quizartinib.通过重新利用 FLT3 抑制剂 quizartinib 预防化疗引起的骨髓抑制。
Sci Transl Med. 2017 Aug 9;9(402). doi: 10.1126/scitranslmed.aam8060.
2
Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion.短暂抑制CDK4/6可保护造血干细胞免受化疗诱导的耗竭。
Sci Transl Med. 2017 Apr 26;9(387). doi: 10.1126/scitranslmed.aal3986.
3
An open-label, single-dose, phase 1 study of the absorption, metabolism and excretion of quizartinib, a highly selective and potent FLT3 tyrosine kinase inhibitor, in healthy male subjects, for the treatment of acute myeloid leukemia.一项在健康男性受试者中进行的开放标签、单剂量1期研究,旨在研究用于治疗急性髓性白血病的高度选择性强效FLT3酪氨酸激酶抑制剂quizartinib的吸收、代谢和排泄情况。
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4
Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy.克服针对FLT3的急性髓系白血病治疗中因合成致死毒性导致的骨髓抑制。
Elife. 2014 Dec 22;3:e03445. doi: 10.7554/eLife.03445.
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Antineoplastic agents and the associated myelosuppressive effects: a review.抗肿瘤药物及其相关的骨髓抑制作用:综述
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6
Flt3 inhibitor AC220 is a potent therapy in a mouse model of myeloproliferative disease driven by enhanced wild-type Flt3 signaling.Flt3 抑制剂 AC220 是一种有效的治疗方法,可用于由增强的野生型 Flt3 信号驱动的骨髓增生性疾病的小鼠模型。
Blood. 2012 Nov 8;120(19):4049-57. doi: 10.1182/blood-2012-06-436675. Epub 2012 Sep 18.
7
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).AC220是一种独特的强效且选择性的FLT3抑制剂,用于治疗急性髓系白血病(AML)。
Blood. 2009 Oct 1;114(14):2984-92. doi: 10.1182/blood-2009-05-222034. Epub 2009 Aug 4.