Abstract
The bone marrow (BM) microenvironment in hematological malignancies (HMs) comprises heterogeneous populations of neoplastic and nonneoplastic cells. Cancer stem cells (CSCs), neoplastic cells, hematopoietic stem cells (HSCs), and mesenchymal stromal/stem cells (MSCs) are all components of this microenvironment. CSCs are the HM initiators and are associated with neoplastic growth and drug resistance, while HSCs are able to reconstitute the entire hematopoietic system; finally, MSCs actively support hematopoiesis. In some HMs, CSCs and neoplastic cells compromise the normal development of HSCs and perturb BM-MSCs. In response, “reprogrammed” MSCs generate a favorable environment to support neoplastic cells. Extracellular vesicles (EVs) are an important cell-to-cell communication type in physiological and pathological conditions. In particular, in HMs, EV secretion participates to unidirectional and bidirectional interactions between neoplastic cells and BM cells. The transfer of EV molecular cargo triggers different responses in target cells; in particular, malignant EVs modify the BM environment in favor of neoplastic cells at the expense of normal HSCs, by interfering with antineoplastic immunity and participating in resistance to treatment. Here, we review the role of EVs in BM cell communication in physiological conditions and in HMs, focusing on the effects of BM niche EVs on HSCs and MSCs.
Highlights
Normal hematopoietic stem cells (HSCs) reside in bone marrow (BM) and are supported by specialized and strictly organized stem cell niches, like endosteal and vascular [1]
Genetic alterations in HSCs or progenitors are associated to several hematologic malignancies (HMs) such as myelodysplastic syndrome (MDS), myeloproliferative neoplasia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia [3]
leukemia stem cells (LSCs) reside in the same niche as healthy HSCs and, on one side, they benefit from BM niche support and, on the other side, they modify the BM niche in order to induce a favorable environment for leukemic growth hampering normal hematopoiesis [5]
Summary
Normal hematopoietic stem cells (HSCs) reside in bone marrow (BM) and are supported by specialized and strictly organized stem cell niches, like endosteal and vascular [1]. Studying the crosstalk between HSCs, LSCs, hematological neoplastic cells, and the BM microenvironment will enhance our comprehension of some human diseases including several HMs and the discovery of new potential therapies. Since EVs are present in biological fluids such as blood, urine, and sperm, [18, 19] and are a representative part of the whole cell for their phenotype and content, they could be used as a diagnostic tool by mimicking a “liquid biopsy.” These last characteristics make them excellent candidates as diagnostic and/or prognostic biomarkers in different diseases, especially in tumors, through noninvasive or minimally invasive procedures. We will discuss the recent advances in the field of EVs as actors in communication between cells within the BM niche in physiological conditions and in HMs, underlining the role and the effects in the tumor microenvironment-stem cell crosstalk. We will focus on the effects of EVs from BM niche cells on HSCs and MSCs
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