Figure 1.

Quantifiable immune factors and other factors affecting leukemic relapse that can be used to increase MFC-MRD accuracy. (Created with BioRender.com, (Accessed on 8 August 2022)). Multiparametric flow cytometry can accurately assess post-treatment qualitative and quantitative alterations in immune and leukemic cell and bone marrow cytokines. Treatment with the hypomethylating agent azacytidine can modulate the signal transducer and activator of transcription (STAT) architecture in both CD4⁺ and CD34⁺ cells, while the bcl-2 inhibitor venetoclax can increase reactive oxygen species generation and boost the antileukemic activity of CD8⁺ and CD4/CD8 double-negative T cells. Conventional chemotherapy, on the other hand, leads to the emergence of a phenotypically and molecularly distinct subpopulation of leukemia-regenerating cells which cannot be traced with the current panels of MFC-MRD. Finally, relapse after allogeneic transplantation appears to be driven by epigenetic alterations in leukemic stem cells resulting in deregulation of the immune pathways involved in antigenic presentation and T cell co-stimulation.