Glutamine requirements for purine metabolism in leukemic lymphoblasts

The two pathways of purine metabolism that include glutamine-dependent reactions, purine synthesis de novo and guanine nucleotide synthesis, were studied in cultured lymphoblasts derived from patients with T cell (JM), B cell (BALL) or null cell (NALL) acute lymphoblastic leukemia (ALL). When glutamine was omitted from the incubation medium, purine synthesis de novo, measured by the incorporation of 14C-formate into purine compounds, was depressed to barely measurable rates in BALL and NALL cells, but proceeded at moderate though reduced rates in JM cells, when compared to synthesis in the presence of 2 mM glutamine. Similarly, the incorporation of 14C-hypoxanthine into guanine nucleotides was arrested at the glutamine-requiring XMP-aminase reaction in the BALL and NALL lines but not in the JM line, when exogenous glutamine was absent. The data suggest that glutamine deprivation, whether by omission from the culture medium in vitro or by glutaminase treatment in vivo, will have more profound biochemical consequences in B and null cell-derived ALL than in T All.