Fig. 5: Intrinsic VEN-resistant PDX samples show elongated mitochondrial structures and increased mitochondrial DNA content. | Cell Death & Disease

Fig. 5: Intrinsic VEN-resistant PDX samples show elongated mitochondrial structures and increased mitochondrial DNA content.

From: Venetoclax resistance in acute lymphoblastic leukemia is characterized by increased mitochondrial activity and can be overcome by co-targeting oxidative phosphorylation

Fig. 5

A Mitochondrial morphology of three sensitive and three highly VEN-resistant PDX samples were analyzed by electron microscopy imaged in a JEM-1400 TEM (Jeol). B The mitochondrial length/width ratio of 83 cells (661 and 756 Mitochondria) was analyzed using the ImageJ software. Chi-square analysis comparing the distribution of elongated mitochondria in VENsens and VENins PDX samples is shown. C Mitochondrial DNA content was assessed by relative quantification and correlated to VEN EC50 values (Spearman correlation; r, correlation coefficient; p, significance). D Western Blot analysis of OPA1 and DRP1 is shown comparing three VEN-sensitive and three VEN-resistant PDX samples. Protein expression was normalized to tubulin using ImageJ analysis. E Three VEN-sensitive and three highly VEN-resistant PDX samples ( > 1 µM EC50) were incubated with increasing concentrations of Staurosporine (DMSO; 1 nM; 10 nM; 50 nM; 100 nM; 500 nM) for 24 h. Relative cell death rates were assessed by propidium iodide (PI) staining and normalized to DMSO controls. (N = 1 technical triplicates).

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