Fig. 3

The antiproliferative effect of inhibitors of glycolysis, lactate transport and the pentose phosphate pathway in subsets of AML patients. a The antiproliferative effects of three inhibitors (lonidamine, AZD3965, and 6-AN) were compared for patients showing high and low insulin-induced pathway activation (Fig. 1, cluster I, versus Fig. 1, cluster II-IV, respectively). AZD3965 had a significantly weaker antiproliferative effect on AML cells, whereas the effects of the two other inhibitors did not differ significantly (data not shown). b A cluster analysis was performed based on the two Akt phosphorylation sites and that of its immediate downstream mediator mTOR (mTOR pS2448). Hierarchical clustering was performed by Pearson’s correlation and weighted pair group method with arithmetic mean as to measure distance. The Mann–Whitney U-test was used to compare different groups. Red indicates high phosphorylation/expression, and blue indicates low phosphorylation/expression. Two main clusters were identified, referred to as cluster I and cluster II. Patients (16 out of 27) from Fig. 1/cluster I (generally strong insulin effect) were included in the lower main cluster I (black dots), with subcluster IB showing the strongest insulin effect. c The effects of lonidamine, AZD3965, and 6-AN were measured for patients showing insulin-induced activation of Akt and mTOR (Fig. 3b, clusters I and II)