Natural compounds and pharmaceuticals reprogram leukemia cell differentiation pathways

In addition to apoptosis resistance and cell proliferation capacities, the undifferentiated state also characterizes most cancer cells, especially leukemia cells. Cell differentiation is a multifaceted process that depends on complex regulatory networks that involve transcriptional, post-transcriptional and epigenetic regulation of gene expression. The time- and spatially-dependent expression of lineage-specific genes and genes that control cell growth and cell death is implicated in the process of maturation. The induction of cancer cell differentiation is considered an alternative approach to elicit cell death and proliferation arrest. Differentiation therapy has mainly been developed to treat acute myeloid leukemia, notably with all-trans retinoic acid (ATRA). Numerous molecules from diverse natural or synthetic origins are effective alone or in association with ATRA in both in vitro and in vivo experiments. During the last two decades, pharmaceuticals and natural compounds with various chemical structures, including alkaloids, flavonoids and polyphenols, were identified as potential differentiating agents of hematopoietic pathways and osteogenesis. •Differentiation is a therapeutic target in leukemia.•Phytochemicals and pharmaceuticals act as differentiating agents of acute and chronic leukemia cells.•All-trans retinoic acid-mediated differentiation is potentiated by natural compounds.•Natural compounds induce osteoblast differentiation of human bone marrow stromal cells related to multiple myeloma.•Plant extracts continuously reveal novel and promising anticancer properties for future cancer therapies.