To date we can identify the main mechanisms involved (Figure 2): occurrence of Bcl-2 mutations (e.g., Gly101Va) that cause a reduction in Venetoclax affinity for Bcl-2 [117], upregulation of other anti-apoptotic proteins like BCL-XL or MCL-1, which can provide alternative survival signals for the leukemia cells [118], reduced expression of pro-apoptotic proteins crucial for Venetoclax-induced apoptosis [119], and increased OXPHOS or alternative sources for energy metabolism [120]. This evidence concerns the gene BCL2 and leukemia.