Dietary thiamine influences l-asparaginase sensitivity in a subset of leukemia cells

Rohiverth Guarecuco, Robert T. Williams, Lou Baudrier, Konnor La, Maria C. Passarelli, Naz Ekizoglu, Mert Mestanoglu, Hanan Alwaseem, Bety Rostandy, Justine Fidelin, Javier Garcia-Bermudez, Henrik Molina (+1 others)
2020 Science Advances  
Tumor environment influences anticancer therapy response but which extracellular nutrients affect drug sensitivity is largely unknown. Using functional genomics, we determine modifiers of l-asparaginase (ASNase) response and identify thiamine pyrophosphate kinase 1 as a metabolic dependency under ASNase treatment. While thiamine is generally not limiting for cell proliferation, a DNA-barcode competition assay identifies leukemia cell lines that grow suboptimally under low thiamine and are
more » ... amine and are characterized by low expression of solute carrier family 19 member 2 (SLC19A2), a thiamine transporter. SLC19A2 is necessary for optimal growth and ASNase resistance, when standard medium thiamine is lowered ~100-fold to human plasma concentrations. In addition, humanizing blood thiamine content of mice through diet sensitizes SLC19A2-low leukemia cells to ASNase in vivo. Together, our work reveals that thiamine utilization is a determinant of ASNase response for some cancer cells and that oversupplying vitamins may affect therapeutic response in leukemia.
doi:10.1126/sciadv.abc7120 pmid:33036978 fatcat:f3hfvpsdsbh4zcqiyll5umdkau