Myelodysplastic syndrome (MDS) is a rare form of blood cancer that can predispose individuals to acute myelodysplastic leukaemia. New treatment options aim to inhibit the action of CD47, an anti-phagocytic signal that increases in number as MDS progresses and prevents phagocytosis of leukemic cells. These treatments, however, have faced limited success in late stage MDS patients. It is theorised that the poor response rate is caused by a phenotypic shift in the macrophage population; becoming more anti-inflammatory because of a tumour-created micro-environment, as evidenced by Yang et al (2021). In this project, we aimed to use Venetoclax; a drug which could potentially shift the overall macrophage population to a pro-inflammatory M1 state, from an unpolarised M0 state or an anti-inflammatory M2 state to support anti-CD47 MDS treatment. We measured the impact of Venetoclax on the metabolic activity of the macrophages and utilised flow cytometry to measure specific cell markers to identify shifts in macrophage phenotype. Our results indicated that Venetoclax is minimally toxic to macrophages at concentrations around 1-2nM – when drugged with Venetoclax, the M0 macrophage population did shift, but not to an M1 phenotype, with the result of the transformation remaining unknown. However, Venetoclax does alter the M2 phenotype to an M1 state; ideal for a potential MDS co-treatment if further repeats and patient trials prove so.
Joshua Watts (2026) studied this question.