Understanding the interaction between leukaemia stem cells and their microenvironment to improve therapeutic approaches

Abstract

Although chemotherapeutic regimens can eliminate blasts in leukaemia patients, such therapies are associated with toxicity and often fail to eliminate all malignant cells resulting in disease relapse. Disease relapse has been attributed to the persistence of leukaemia cells in the bone marrow (BM) with the capacity to recapitulate disease; these cells are often referred to as leukaemia stem cells (LSCs). Although LSCs have distinct characteristics in terms of pathobiology and immunophenotype, they are still regulated by their interactions with the surrounding microenvironment. Thus, understanding the interaction between LSCs and their microenvironment is critical to identify effective therapies. To this end, there are numerous efforts to develop models to study such interactions. In this review, we will focus on the reciprocal interactions between LSCs and their milieu in the BM. Furthermore, we will highlight relevant therapies targeting these interactions and discuss some of the promising in vitro models designed to mimic such relationship.

Cancer microenvironment and pharmacological interventions

“…Two-dimensional model systems overestimate therapeutic efficacy (Dainiak et al, 2008), failing to translate into clinical efficacy. Furthermore, xenograft mouse models lack a functional immune system, with findings generated from these models not directly applicable to humans, as human cancer cellhuman TME interactions differ from human cancer cell-murine TME interactions at the cellular and molecular level (Martinez & Guzman, 2023). Three-dimensional model systems incorporating TME-resident cells (e.g., X, Y, Z) and extracellular matrix (ECM) components hold much promise (Nyamondo & Wheadon, 2023) as they more accurately reflect TME features, such as hypoxia and reactive oxygen species, not present in most 2D models.…”