Leukemic Transdifferentiation: From Pathological Plasticity to Dendritic Cell-Based Immunotherapy

Transdifferentiation, also known as direct reprogramming, is the transformation of one terminally differentiated cell type into another mature cell type, while bypassing the stage of pluripotency. In leukemia, this phenomenon has a dual significance: on the one hand, it is an adaptive mechanism driving tumor survival and resistance to treatment, and on the other, it offers a potential opportunity for innovative therapies. Of particular interest is the directional transdifferentiation (mostly partial) toward dendritic cell-like phenotypes, which increases the immunogenicity of cancer cells. Mastering this process could define a new generation of immunotherapies that leverage the inherent plasticity of leukemic cells to achieve therapeutic benefits. In this brief review, we attempt to gather information concerning the molecular mechanism of this process and point to the role of dendritic cells as a crucial element of anticancer, particularly anti-leukemia innate and acquired, immunity. Thus, in vitro and in vivo techniques of inducing transformation of the leukemia cells into cancer antigen-presenting cells and the application of these technologies in current and future therapies are discussed.