Vitamin B6 Addiction in Acute Myeloid Leukemia

Cancer cells rely on altered metabolism to support their proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting a library of metabolic enzymes and identified PDXK - the enzyme that produces pyridoxal phosphate (PLP) from vitamin B6 - as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity was required for both PLP production and AML cell proliferation. Additionally, pharmacological blockade of the vitamin B6 pathway recapitulated PDXK disruption. Metabolomic profiling revealed AML cells have unique dependencies on vitamin B6-dependent metabolic reactions and disruption of this metabolism impaired their proliferation. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.

 

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