RESUMO
Stem cells experience many selective pressures which shape their cellular populations, potentially pushing them to skew towards dominance of a few break-through clones. An evolutionarily conserved answer to curb these aberrant selective pressures is cell competition, the elimination of a subset of cells by their neighbours in a seemingly homogenous population. Cell competition in mammalian systems is a relatively recent discovery that has now been observed across many tissue systems, such as embryonic, haematopoietic, intestinal, and epithelial compartments. With this rapidly growing field, there is a need to revisit and standardize the terminology used, much of which has been co-opted from evolutionary biology. Further, the implications of cell competition across biological scales in organisms have been difficult to capture. In this review, we make three key points. One, we propose new nomenclature to standardize concepts across dispersed studies of different types of competition, each of which currently use the same terminology to describe different phenomena. Second, we highlight the challenges in capturing information flow across biological scales. Third, we challenge the field to incorporate next generation technologies into the cell competition toolkit to bridge these gaps. As the field of cell competition matures, synergy between cutting edge tools will help elucidate the molecular events which shape cellular growth and death dynamics, allowing a deeper examination of this evolutionarily conserved mechanism at the core of multicellularity.
RESUMO
Acute myeloid leukemia (AML) is an aggressive blood malignancy characterized by the accumulation of immature blood cells that can severely impede the normal functions of the hematopoietic system. AML still has a poor 5-year survival rate of around 30%, and efforts to develop novel targeted therapies have been met with challenges. Allogeneic hematopoietic stem cell transplantation represents a potentially curative treatment for many AML patients. Donor immune cells, namely, T cells and NK cells, can help eliminate residual leukemia cells through the beneficial graft-versus-leukemia (GVL) effect. Nevertheless, malignant cells can still escape allogeneic immune surveillance and lead to disease relapse. Recent studies have provided insights into AML-specific immune evasion mechanisms, many of which are driven by epigenetic changes. This article describes epigenetic regulators as promising therapeutic targets for designing posttransplant maintenance therapies. Therefore, this review aims to summarize AML immune evasion mechanisms with a focus on the allogeneic immune environment. We discuss the roles of epigenetic regulators in driving immune escape and propose targeted strategies for preventing leukemia relapse. We then discuss the diverse immunomodulatory effects of epigenetic inhibitors and their potential to enhance the GVL effect. The current landscape of maintenance therapy trials with epigenetic inhibitors and their clinical prospects is also assessed.