Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia

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Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia

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作者：David B. Sykes¹ ; ² ; ¹¹ ; ¹² ; ¹⁵ ; ^{dbsykes@mgh.harvard.edu" class="auth_mail" title="E-mail the corresponding author} ; Youmna S. Kfoury¹ ; ¹¹ ; ¹² ; Fran&ccedil ; ois E. Mercier¹ ; ¹¹ ; ¹² ; Mathias J. Wawer³ ; Jason M. Law⁴ ; ¹³ ; Mark K. Haynes⁵ ; Timothy A. Lewis⁴ ; Amir Schajnovitz¹ ; ¹¹ ; ¹² ; Esha Jain¹ ; Dongjun Lee¹ ; ¹¹ ; ¹² ; Hanna Meyer⁶ ; Kerry A. Pierce⁷ ; Nicola J. Tolliday³ ; Anna Waller⁵ ; Steven J. Ferrara³ ; Ashley L. Eheim⁶ ; Detlef Stoeckigt⁶ ; Katrina L. Maxcy¹ ; Julien M. Cobert¹ ; Jacqueline Bachand¹ ; Brian A. Szekely¹ ; Siddhartha Mukherjee⁸ ; Larry A. Sklar⁵ ; Joanne D. Kotz⁴ ; Clary B. Clish⁷ ; Ruslan I. Sadreyev⁹ ; ¹⁰ ; Paul A. Clemons⁴ ; Andreas Janzer⁶ ; Stuart L. Schreiber⁴ ; ¹³ ; ¹⁴ ; David T. Scadden¹ ; ² ; ¹¹ ; ¹² ; ^{dscadden@mgh.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
关键词：acute myeloid leukemia ; differentiation ; HoxA9 ; high-throughput screen ; phenotypic screen ; leukemia-initiating cell ; dihydroorotate dehydrogenase ; brequinar ; metabolic inhibitor
刊名：Cell
出版年：2016
出版时间：22 September 2016
年：2016
卷：167
期：1
页码：171-186.e15
全文大小：4665 K

文摘

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A phenotypic differentiation screen identifies DHODH as a target in AML

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DHODH is a key link between pyrimidine synthesis and myeloid differentiation

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DHODH represents a metabolic vulnerability across a range of AML subtypes

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DHODH inhibitors show therapeutic potential in preclinical AML models.

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