Dietary thiamine influences l-asparaginase sensitivity in a subset of leukemia cells. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • October 9, 2020

Research

keywords

  • Antineoplastic Agents
  • Leukemia

Identity

PubMed Central ID

  • PMC7546708

Scopus Document Identifier

  • 85092752443

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abc7120

PubMed ID

  • 33036978

Additional Document Info

volume

  • 6

issue

  • 41