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. Author manuscript; available in PMC: 2018 Jul 26.
Published in final edited form as: Blood. 2018 Feb 20;131(15):1639–1653. doi: 10.1182/blood-2017-12-820035

Figure 5. Combined effects of tyrosine kinase inhibitors and CB839 in BCR-ABL positive leukemia.

Figure 5

(A) Glycolytic rate and capacity of BCR-ABL mutated K562 cells treated with vehicle control or Imatinib 2 µM (mean ± s.e.m., n=3, P<0.0001 for both glycolytic rate and capacity, respectively, two-way ANOVA with Bonferroni’s multiple comparison) (B) Volcano plot for gene expression changes by RNA-sequencing of K562 cells treated with Imatinib 2 µM or vehicle control highlighting reduced expression of genes involved in glycolysis in treated cells (n=2). (C) q-PCR validation in K562 cells for the reduction in expression levels of GLUT3 (mean ± s.e.m., n=3, ** P=0.0081, two-tailed paired t-test) and LDHA (mean ± s.e.m., n=3, * P=0.0132, two-tailed paired t-test) following treatment as in (B). (D) Apoptosis in K562 cells treated with vehicle control, Imatinib 2 µM, CB839 100 nM, Imatinib and CB839 combination and Imatinib/CB839 combination + 4 mM αKG (mean ± s.e.m., n=9, ** P=0.0019 between Imatinib versus Imatinib+CB839, and **** P<0.0001 between Imatinib+CB839 versus Imatinib+CB839+αKG, ANOVA with Tukey’s multiple comparisons) (E) Relative cytoplasmic ROS levels in BCR-ABL mutated K562 cells treated as in (D) (mean ± s.e.m., n=6, * P=0.0495 between Imatinib versus Imatinib+CB839, and ** P=0.0089 between Imatinib+CB839 versus Imatinib+CB839+αKG, ANOVA with Sidak’s multiple comparisons). (F) Oxygen consumption rate in K562 cells treated as in (D) (mean ± s.e.m., n=3, for basal respiration P=0.0606 between Imatinib versus Imatinib+CB839, and P<0.0001 between Imatinib+CB839 versus Imatinib+CB839+aKG, for maximal respiration between **** P<0.0001 between both Imatinib versus Imatinib+CB839 and Imatinib+CB839 versus Imatinib+CB839+αKG, two-way ANOVA with Bonferroni’s multiple comparisons).