Vitamin B6 Addiction in Acute Myeloid Leukemia.

Clicks: 266
ID: 80646
2020
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Abstract
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.
Reference Key
chen2020vitamincancer Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Chen, Chi-Chao;Li, Bo;Millman, Scott E;Chen, Cynthia;Li, Xiang;Morris, John P;Mayle, Allison;Ho, Yu-Jui;Loizou, Evangelia;Liu, Hui;Qin, Weige;Shah, Hardik;Violante, Sara;Cross, Justin R;Lowe, Scott W;Zhang, Lingbo;
Journal cancer cell
Year 2020
DOI
S1535-6108(19)30572-0
URL
Keywords
therapeutic target pyridoxal phosphate acute myeloid leukemia abt-199/venetoclax b cell lymphoma-2 crispr/cas9 functional genomics plp-dependent enzyme pyridoxal kinase selective metabolic dependency vitamin b6

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