Acute Myeloid Leukemia (AML) is a hematological malignancy in which there’s an overproliferation of immature myeloid cells. AML is commonly treated with the BCL2 inhibitor Venetoclax, but ~30% of patients fail to respond and most eventually become resistant. One mechanism of resistance to Venetoclax is mitophagy, the digestion of damaged mitochondria, which is regulated by alternative splicing of the poison intron 6 in the PINK1 gene by GSK-3. We hypothesized that the inhibition of GSK-3 with the drug CHIR99021 (CHIR) would enhance the sensitivity of AML cells to Venetoclax by limiting mitophagy through PINK1 splicing. Three AML cell lines of MV4-11, OCI-AML3, and MOLM-13 were treated every other day with varying concentrations of Venetoclax with and without CHIR and counted on Day 6 with a hemocytometer. Cells treated with both drugs had lower cell proliferation than cells treated with only Venetoclax, seen most significantly in MV4-11. Flow cytometry detection of apoptosis with 7-AAD and Annexin V staining was conducted on Day 6. Cells treated with both drugs had higher levels of apoptosis for MV4-11 and MOLM-13 but not for OCI-AML3. These data may be less significant than cell proliferation because most cells were already dead by Day 6. Lastly, agarose gels were run with DNA acquired from purifying RNA on Day 4, treating with DNAse, reverse transcribing, and performing PCR with primers from Exon 6 and 7 of PINK1 to visualize splicing. Percent intron retention was calculated through ImageJ analysis of grayscale levels. PINK1 splicing increased with Venetoclax treatment and decreased with CHIR treatment for all cell lines, indicating a mitophagy response by cells to Venetoclax and an inhibition by CHIR. Overall, these data support our hypothesis that inhibition of mitophagy with CHIR enhances cell sensitivity to Venetoclax.