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 ; Franç ; 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.