期刊
CANCER CELL
卷 37, 期 1, 页码 71-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2019.12.002
关键词
-
资金
- CSHL President's Council
- NIH/NCI [P30 CA045508, R01 CA190261]
- Northwell Cancer Translational Research grant
- NIH/NHLBI grant [U01 HL127522]
- Edward P. Evans Foundation EvansMDS Young Investigator Award
- Agilent Thought Leader Award
- MSKCC cancer center support grant [P30 CA008748]
Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK-an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6-as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. PDXK disruption reduced intracellular concentrations of key metabolites needed for cell division. Furthermore, disruption of PLP-dependent enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products partially rescued PDXK disruption induced proliferation blockage. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据