Mesenchymal Stromal Cells (MSCs): An Ally of B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells in Disease Maintenance and Progression within the Bone Marrow Hematopoietic Niche

Abstract

Mesenchymal stromal cells (MSCs) are structural components of the bone marrow (BM) niche, where they functionally interact with hematopoietic stem cells and more differentiated progenitors, contributing to hematopoiesis regulation. A growing body of evidence is nowadays pointing to a further crucial contribution of MSCs to malignant hematopoiesis. In the context of B-cell acute lymphoblastic leukemia (B-ALL), MSCs can play a pivotal role in the definition of a leukemia-supportive microenvironment, impacting on disease pathogenesis at different steps including onset, maintenance and progression. B-ALL cells hijack the BM microenvironment, including MSCs residing in the BM niche, which in turn shelter leukemic cells and protect them from chemotherapeutic agents through different mechanisms. Evidence is now arising that altered MSCs can become precious allies to leukemic cells by providing nutrients, cytokines, pro-survivals signals and exchanging organelles, as hereafter reviewed. The study of the mechanisms exploited by MSCs to nurture and protect B-ALL blasts can be instrumental in finding new druggable candidates to target the leukemic BM microenvironment. Some of these microenvironment-targeting strategies are already in preclinical or clinical experimentation, and if coupled with leukemia-directed therapies, could represent a valuable option to improve the prognosis of relapsed/refractory patients, whose management represents an unmet medical need.

BM-MSCs display altered gene expression profiles in B-cell acute lymphoblastic leukemia niches and exert pro-proliferative effects via overexpression of IFI6

“…TME has been reported to function crucially in the occurrence and development of leukemia [ 19 – 21 ]. BM-MSCs, as a pivotal microenvironmental constituent of bone marrow, are the main factor promoting leukemia progression in the TME [ 22 , 23 ]. However, it remains unclear what changes have taken place in MSCs in the B-ALL niches.…”

Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia

“…MSCs in B-ALL are known for their altered functionality and molecular profiles, particularly in their interactions with leukemic cells. These interactions involve various mechanisms, including the secretion of cytokines and chemokines, adhesion molecule interactions, and the transfer of metabolites and organelles [ 87 , 88 ].…”

“…A key aspect of MSCs in B-ALL is their ability to create a leukemia-supportive microenvironment. This includes the production of inflammatory mediators and transforming growth factor-β (TGF-β) family molecules, which can promote leukemic cell survival and progression [ 87 ]. MSCs also contribute to chemokine axis alterations within the BM niche, notably affecting the CXCL12/CXCR4 axis, which is crucial for leukemic cell homing and proliferation [ 89 ].…”

“…Fallati, A. et al [87] MSCs contribute to B-ALL pathogenesis and progression by creating a leukemia-supportive BM microenvironment rich in TGF-β molecules and inflammatory mediators.…”

Dynamic evolution of bone marrow adipocyte in B cell acute lymphoblastic leukemia: insights from diagnosis to post-chemotherapy

“…MSCs have long been recognized as a major component of the BMM, promoting leukemia cell proliferation and chemoresistance. 10 , 11 Conversely, adipocytes, a distinctive and versatile component of the BMM, have only recently gained prominence after being overlooked for a significant period. 12 Accumulating evidence suggests that adipocytes also influence the proliferation of leukemic blasts.…”