The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome

Abstract

This research investigated the level of glycolytic metabolism in leukemic blasts as a prognostic marker in AML. Using an in vitro dye-reduction assay, we determined the level of glycolytic metabolism in 26 BM samples taken from 23 adult patients with newly diagnosed (n=19) or relapsed (n=4) AML, and AML blasts stratified into two distinct cohorts of moderate (<70%) or high (>80%) levels of glycolytic metabolism. All samples taken at relapse were moderately glycolytic. However, nine of the 19 samples taken at diagnosis were highly glycolytic, and 10 were moderately glycolytic. Three patients had paired samples taken at diagnosis and relapse, and the glycolytic metabolism of these samples did not alter between the two time-points. The level of glycolytic metabolism did not correlate with the percentage of marrow blasts, patient age, or CG/molecular risk group. Highly glycolytic AML blasts were more resistant to apoptosis induced by ATRA and/or ATO in vitro, suggesting potential resistance to induction chemotherapy, as has been observed in solid tumors. Despite this, high levels of glycolytic metabolism at diagnosis were predictive of a significantly improved duration of CR1 and OS following AML remission induction chemotherapy. In conclusion, we found that the extent of myeloblast glycolysis may be an effective and easily applied method to determine the pretreatment prognosis of AML.