PT  - JOURNAL ARTICLE
AU  - Guarecuco, Rohiverth
AU  - Williams, Robert T.
AU  - Baudrier, Lou
AU  - La, Konnor
AU  - Passarelli, Maria C.
AU  - Ekizoglu, Naz
AU  - Mestanoglu, Mert
AU  - Alwaseem, Hanan
AU  - Rostandy, Bety
AU  - Fidelin, Justine
AU  - Garcia-Bermudez, Javier
AU  - Molina, Henrik
AU  - Birsoy, Kıvanç
TI  - Dietary thiamine influences <span class="sc">l</span>-asparaginase sensitivity in a subset of leukemia cells
AID  - 10.1126/sciadv.abc7120
DP  - 2020 Oct 01
TA  - Science Advances
PG  - eabc7120
VI  - 6
IP  - 41
4099  - http://advances.sciencemag.org/content/6/41/eabc7120.short
4100  - http://advances.sciencemag.org/content/6/41/eabc7120.full
SO  - Sci Adv2020 Oct 01; 6
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.