ABSTRACT

Venetoclax in combination with Azacitidine has demonstrated the ability to regulate cell survival, with tolerable safety and favourable overall responses in older adult patients with AML. This novel combination regimen has shown efficacy even in high risk groups, such as those aged 75 or older, patients with poor cytogenetics, and those with secondary AML. The addition of Venetoclax enhanced the effect of Azacitidine on in vivo survival, and this combination has been effective in disrupting the metabolic machinery that drives energy metabolism, leading to the eradication of leukemia stem cells. In this study, the growth of hematopoietic and leukemic stem cells were analyzed using a mathematical model that considers the bone marrow as a system of "well-mixed" tanks of cells at different stages of differentiation. Mathematical analysis focused on parameters such as self-renewal, proliferation, and apoptosis, assessing the impact of Venetoclax in combination with Azacitidine. The B-cell lymphoma 2 (BCL-2) protein is critical for the survival and persistence of AML blasts, and Venetoclax targets this protein to regulate cell survival. In AML, overexpression of BCL-2 contributes to the survival of leukemic cells, including AML blasts. Azacitidine, on the other hand, works by inhibiting DNA methylation and promoting cell death. Overall, the combination of Venetoclax and Azacitidine offers a promising therapeutic approach for AML, particularly in older adults and high risk patient groups. By targeting key pathways involved in cell survival and metabolism, this combination regimen holds potential for improving outcomes in AML patients. Keywords: Venetoclax; Azacitidine; Acute Myeloid Leukaemia (AML); Hematopoietic Stem Cells (HSC); Leukemic Stem Cells (LSC)
Publication date: 01/06/2024

https://ijbpas.com/pdf/2024/June/MS_IJBPAS_2024_8960.pdf

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https://doi.org/10.31032/IJBPAS/2024/13.6.8960