Fig. 3: Aberrant PI3K signaling polarizes leukemia metabolism towards glycolysis.

A Glucose uptake in T-ALL cell lines. Each dot represents a replicate. Box plots show minima, maxima, median, and 25% and 75% percentiles. B Cell viability at 72 h of wild-type and PI3K-altered T-ALL cell lines under complete culture conditions or without glucose (mean ± SEM are indicated per cell line from three replicates in three independent experiments). C Glucose uptake in wild-type (n = 9 individual PDX) and PI3K-altered (n = 12 individual PDX) T-ALL PDX. Box plots show minima, maxima, median, and 25% and 75% percentiles. An unpaired Welch-corrected two-tailed t-test was run (***, p < 0.001). D Pearson correlations between phosflow p-Akt or p-S6 and glucose uptake levels in wild-type (n = 14 individual PDX) PI3K-altered (n = 8 individual PDX) T-ALL PDX. The SEM is indicated by the gray area. E Glucose uptake in PI3K-altered PDX was measured at 72 h upon PI3K signaling inhibition (n = 8 individual PDX). Box plots show minima, maxima, median, and 25% and 75% percentiles. A one-way ANOVA test adjusted for multiple comparisons (Dunn–Šidák correction) was run (*, p < 0.05; ***, p < 0.001). F Cell viability at 72 h of PI3K-altered PDX was measured upon PI3K signaling (mean ± SEM, n = 8 individual PDX). A one-way ANOVA adjusted for multiple comparisons (Dunn’s test) was performed (ns, p > 0.05). G Cell viability at 72 h of wild-type and PI3K-altered T-ALL PDX under complete culture conditions or without glucose (n = 18 individual PDX evaluated in duplicates). H Cell proliferation of CellTrace-labelled wild-type and PI3K-altered T-ALL PDX was evaluated after 72 h in complete culture condition or without glucose (mean ± SEM, n = 4 individual PDX). Each generation was defined by a CellTrace peak. I Phosflow evaluation of PI3K signaling activity in wild-type (n = 14) and PI3K-altered (n = 8) blasts cultured for 72 h in complete medium or without glucose. Box plots show minima, maxima, median, and 25% and 75% percentiles. J ATP levels in PI3K-altered PDX were evaluated after 72 h in complete culture condition or without glucose (n = 8 individual PDX) by LC/MS. Relative abundances are indicated. Box plots show minima, maxima, median, and 25% and 75% percentiles. An unpaired homoscedastic two-tailed t-test was performed (ns, p > 0.05).