Date: October 1, 2020
Time: 11:00am (PDT), 2:00pm (EDT)
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.
- Attendees will gain an understanding of how Crispr/Cas9 screening can be used to identify metabolic vulnerabilities in cancer cells.
- Attendees will gain an appreciation of the spectrum of vitamin B6-dependent metabolic reactions.
- Attendees will learn how a combination of genetic and pharmacological approaches can be used in conjunction with LC-MS profiling and stable isotope tracing to investigate a metabolic pathway utilization
For Research Use Only. Not for use in diagnostic procedures.
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