The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Catani, Lucia; Cavo, Michèle; Palandri, Francesca

doi:10.3390/cells10092316

Cited by 8 publications

(6 citation statements)

References 120 publications

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“…EVs are known as a heterogeneous population of nano to micro-sized lipid bilayer particles released by most cell types. The EVs derived from blood cells have been validated for their potential role in MPN disease regulation, specifically their orchestration between the MPN clone and the microenvironment [ 145 , 146 ]. In many studies, blood cancer cell-derived EVs have been seen in the functional regulation of important activities, such as chemoresistance, immune regulation, and coagulation cascade.…”

Section: Extracellular Vesicles (Evs) and Circulating Endothelial Cel...mentioning

confidence: 99%

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Bhuria

Baldauf

Schraven

et al. 2022

IJMS

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Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia. The chronic inflammatory syndrome in MPNs is associated with the up-regulation of various inflammatory cytokines in patients and is involved in the formation of the so-called MPN thromboinflammation. JAK2-V617F, the most prevalent mutation in MPNs, has been shown to activate a number of integrins on mature myeloid cells, including granulocytes and erythrocytes, which increase adhesion and drive venous thrombosis in murine knock-in/out models. This review aims to shed light on the current understanding of thromboinflammation, involvement of neutrophils in the prothrombotic state, plausible molecular mechanisms triggering the process of thrombosis, and potential novel therapeutic targets for developing effective strategies to reduce the MPN disease burden.

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Section: Extracellular Vesicles (Evs) and Circulating Endothelial Cel...mentioning

confidence: 99%

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Bhuria

Baldauf

Schraven

et al. 2022

IJMS

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“…Conversely, it is considered that the high PMV levels in children with immune thrombocytopenic purpura restrain the severe bleeding [ 90 ]. In the same context, their accumulation in thrombocytopenia and myeloproliferative neoplasms (despite the low PLT levels) has been linked to hypercoagulable state and thrombotic events [ 91 , 92 , 93 , 94 ], whereas in thrombocythemia constitutes a predisposing factor for venous thrombosis [ 95 , 96 , 97 ] ( Table 3 ). All the aforementioned characteristics highlight their important regulatory role in hemostasis.…”

Section: Platelet Vesiculationmentioning

confidence: 99%

Blood Cell-Derived Microvesicles in Hematological Diseases and beyond

et al. 2022

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Microvesicles or ectosomes represent a major type of extracellular vesicles that are formed by outward budding of the plasma membrane. Typically, they are bigger than exosomes but smaller than apoptotic vesicles, although they may overlap with both in size and content. Their release by cells is a means to dispose redundant, damaged, or dangerous material; to repair membrane lesions; and, primarily, to mediate intercellular communication. By participating in these vital activities, microvesicles may impact a wide array of cell processes and, consequently, changes in their concentration or components have been associated with several pathologies. Of note, microvesicles released by leukocytes, red blood cells, and platelets, which constitute the vast majority of plasma microvesicles, change under a plethora of diseases affecting not only the hematological, but also the nervous, cardiovascular, and urinary systems, among others. In fact, there is evidence that microvesicles released by blood cells are significant contributors towards pathophysiological states, having inflammatory and/or coagulation and/or immunomodulatory arms, by either promoting or inhibiting the relative disease phenotypes. Consequently, even though microvesicles are typically considered to have adverse links with disease prognosis, progression, or outcomes, not infrequently, they exert protective roles in the affected cells. Based on these functional relations, microvesicles might represent promising disease biomarkers with diagnostic, monitoring, and therapeutic applications, equally to the more thoroughly studied exosomes. In the current review, we provide a summary of the features of microvesicles released by blood cells and their potential implication in hematological and non-hematological diseases.

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“…Among them, the increased release of extracellular vesicles (EVs) is associated with inflammation and thrombosis, and sustained malignant haematopoiesis (60,61). Based on this, EVs could represent biomarkers of MPN onset (62), as crucial players in regulating tumour microenvironment through the education of key processes including vascular reactivity, angiogenesis, chemoresistance and immunity. Due to their biocompatibility, small size, ability to cross biological membranes and capacity to target specific cells, EVs also represent a promising new approach for drug delivery (63).…”

Section: A Role For Mscs In Mpnmentioning

confidence: 99%

Bone Marrow Niches and Tumour Cells: Lights and Shadows of a Mutual Relationship

et al. 2022

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The bone marrow (BM) niche is the spatial structure within the intra-trabecular spaces of spongious bones and of the cavity of long bones where adult haematopoietic stem cells (HSCs) maintain their undifferentiated and cellular self-renewal state through the intervention of vascular and nervous networks, metabolic pathways, transcriptional and epigenetic regulators, and humoral signals. Within the niche, HSCs interact with various cell types such as osteoblasts, endothelial cells, macrophages, and mesenchymal stromal cells (MSCs), which maintain HSCs in a quiescent state or sustain their proliferation, differentiation, and trafficking, depending on body needs. In physiological conditions, the BM niche permits the daily production of all the blood and immune cells and their admittance/ingress/progression into the bloodstream. However, disruption of this delicate microenvironment promotes the initiation and progression of malignancies such as those included in the spectrum of myeloid neoplasms, also favouring resistance to pharmacological therapies. Alterations in the MSC population and in the crosstalk with HSCs owing to tumour-derived factors contribute to the formation of a malignant niche. On the other hand, cells of the BM microenvironment cooperate in creating a unique milieu favouring metastasization of distant tumours into the bone. In this framework, the pro-tumorigenic role of MSCs is well-documented, and few evidence suggest also an anti-tumorigenic effect. Here we will review recent advances regarding the BM niche composition and functionality in normal and in malignant conditions, as well as the therapeutic implications of the interplay between its diverse cellular components and malignant cells.

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The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cited by 8 publications

References 120 publications

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Blood Cell-Derived Microvesicles in Hematological Diseases and beyond

Bone Marrow Niches and Tumour Cells: Lights and Shadows of a Mutual Relationship

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