Extended Data Fig. 4: Venetoclax blocks AraC-induced OXPHOS and metabolic phenotypes.
(a) An integrated analysis of IC/MS data based on Metaboanalyst software (pathway tool) for a simplified view of contributing pathways of MOLM14 cells. (b,c) The glycolytic metabolites: glucose 6-phosphate (G6P) (n=6 independent experiments), fructose 6-phosphate (F6P), 2,3-bisphosphoglycerate (2/3PG), amounts (n=3 independent experiments) (b), and the pentose phosphate pathway (PPP) metabolites (n=3 independent experiments): 6-phosphogluconate (6PG), ribose 1-phosphate (Rib1P), sedoheptulose 7-phosphate (Sed7P) amounts (c) measured by IC/MS in MOLM14 cells. Data are represented in fold change to control. P values: G6P, CTL/VEN P=0.3648, CTL/AraC *P=0.0338, CTL/VEN+AraC P=0.1367, AraC/VEN+AraC *P=0.0261; F6P, nsP > 0.1111; 2/3PG, nsP > 0.1111; 6PG, nsP > 0.1111; Rib1P, nsP > 0.1111; Sed7P, nsP > 0.1111; Aspartate, CTL/VEN P=0.0877, CTL/AraC *P=0.0106, CTL/VEN+AraC *P=0.0267, AraC/VEN+AraC *P=0.0170; Glutamate, CTL/VEN P=0.3735, CTL/AraC *P=0.0186, CTL/VEN+AraC P=0.4883, AraC/VEN+AraC P=0.0837. (d) Aspartate and glutamate amount measured by IC/MS in MOLM14 cells. Data are represented in fold change to control. (n=4 independent experiments). (e,f,g) Basal and maximal JATP production in KG1A (e), OCIAML3 (f) and U937 (g) cells, divided into JATPglyc and JATPox using a Seahorse XF24 Extracellular Analyzer. Aggregate data from 4 independent experiments. (h) The contribution of glucose to aspartate and glutamate production in MOLM14 cells (n=2 independent experiments). Data in A, B, C, D, E, F, G, and H are assessed 24H post in vitro treatment with venetoclax (VEN, 0.5 μM) and/or cytarabine (AraC, 0.5 μM). Data in B, C, D, E, F, G, and H are displayed as mean ± s.e.m. Data analysis in B, C and D is by two-tailed paired t-test. *P < 0.05, **P < 0.01, ****P < 0.0001, ns:non-significant.
