RT Journal Article SR Electronic T1 Dietary thiamine influences l-asparaginase sensitivity in a subset of leukemia cells JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eabc7120 DO 10.1126/sciadv.abc7120 VO 6 IS 41 A1 Guarecuco, Rohiverth A1 Williams, Robert T. A1 Baudrier, Lou A1 La, Konnor A1 Passarelli, Maria C. A1 Ekizoglu, Naz A1 Mestanoglu, Mert A1 Alwaseem, Hanan A1 Rostandy, Bety A1 Fidelin, Justine A1 Garcia-Bermudez, Javier A1 Molina, Henrik A1 Birsoy, Kıvanç YR 2020 UL http://advances.sciencemag.org/content/6/41/eabc7120.abstract AB 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 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.