Venetoclax Drives Significant Shifts in BIM and BCL-2 but not MCL-1 Gene Expression in a Mouse Model of Acute Lymphoblastic Leukemia

نویسندگان

1 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

doi
10.30476/mejc.2025.104911.2214
چکیده

Background: T and B acute lymphoblastic leukemia (T, B-ALL) has seen improved survival rates with intensified chemotherapy, but therapy-resistant or refractory ALL remains a significant clinical challenge. This study examined the inhibitory effects of Venetoclax drug on the apoptosis gene to explore its potential as a novel therapeutic approach for treating human T, B-ALL.Method: This was a preclinical experimental study. Firstly, samples were collected from a leukemia patient, followed by isolating blast cells that were injected into primary mice. The sample was obtained from mice in 1, 8 and 14 days; the CD45 human was quantified using flow cytometry to confirm the development of leukemia. Spleen cells from the primary mice were isolated and injected into the secondary mice. After 14 days, the Venetoclax drug was administered to the mouse models for 21 days. Subsequently, mouse spleen cells were gathered, and the expression of genes associated with apoptosis was assessed. A two-tailed t-test was performed to compare the expression of apoptotic genes between the control and Venetoclax-treated groups.Results: Our findings indicated a decrease in the expression of the B-cell lymphoma 2 (BCL-2) gene, while the expression of the BCL-2-interacting mediator (BIM) of cell death gene exhibited an augmentation. The level of expression of the MCL-1 (Myeloid leukemia 1) gene did not display any significant divergence compared with the control group.Conclusion: Venetoclax drug shows potential therapeutic potential in B and T-ALL, increasing BIM expression and decreasing BCL-2, but further investigation and clinical trial studies are needed.