Distinct profile of CD34+ cells and plasma-derived extracellular vesicles from triple-negative patients with Myelofibrosis reveals potential markers of aggressive disease

Autor: Samantha Bruno, Claudio Franceschi, Francesco Fabbri, Giorgia Simonetti, Erika Bandini, Maria Chiara Deregibus, Lucia Catani, Nicola Vianelli, Daria Sollazzo, Dorian Forte, Francesca Palandri, Cristina Morsiani, Emanuela Ottaviani, Michele Cavo, Martina Barone, Giuseppe Auteri, Giovanni Camussi, Miriam Capri, Salvatore Collura
Přispěvatelé: Forte D., Barone M., Morsiani C., Simonetti G., Fabbri F., Bruno S., Bandini E., Sollazzo D., Collura S., Deregibus M.C., Auteri G., Ottaviani E., Vianelli N., Camussi G., Franceschi C., Capri M., Palandri F., Cavo M., Catani L.
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cancer Research
CD34
Inflammation
microRNA
Myelofibrosis
Antigens
CD34
Inflammation
Biology
Severity of Illness Index
lcsh:RC254-282
Immunophenotyping
Proinflammatory cytokine
Flow cytometry
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Progenitor cell
Cells
Cultured
medicine.diagnostic_test
Inflammation
microRNAs
Research
Gene Expression Profiling
Interleukin
Janus Kinase 2
Extracellular vesicles
Hematopoietic Stem Cells
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Mitochondria
Haematopoiesis
030104 developmental biology
Oncology
Primary Myelofibrosis
030220 oncology & carcinogenesis
Mutation
Disease Progression
Cancer research
Cytokines
Female
Tumor necrosis factor alpha
Inflammation Mediators
medicine.symptom
Extracellular vesicle
Biomarkers
Zdroj: Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-14 (2021)
Journal of Experimental & Clinical Cancer Research : CR
ISSN: 1756-9966
Popis: Background Myelofibrosis (MF) is a clonal disorder of hemopoietic stem/progenitor cells (HSPCs) with high prevalence in elderly patients and mutations in three driver genes (JAK2, MPL, or CALR). Around 10–15% of patients are triple-negative (TN) for the three driver mutations and display significantly worse survival. Circulating extracellular vesicles (EVs) play a role in intercellular signaling and are increased in inflammation and cancer. To identify a biomolecular signature of TN patients, we comparatively evaluated the circulating HSPCs and their functional interplay with the microenvironment focusing on EV analysis. Methods Peripheral blood was collected from MF patients (n = 29; JAK2V617F mutation, n = 23; TN, n = 6) and healthy donors (HD, n = 10). Immunomagnetically isolated CD34+ cells were characterized by gene expression profiling analysis (GEP), survival, migration, and clonogenic ability. EVs were purified from platelet-poor plasma by ultracentrifugation, quantified using the Nanosight technology and phenotypically characterized by flow cytometry together with microRNA expression. Migration and survival of CD34+ cells from patients were also analyzed after in vitro treatments with selected inflammatory factors, i.e. (Interleukin (IL)-1β, Tumor Necrosis Factor (TNF)-α, IL6) or after co-culture with EVs from MF patients/HD. Results The absolute numbers of circulating CD34+ cells were massively increased in TN patients. We found that TN CD34+ cells show in vitro defective functions and are unresponsive to the inflammatory microenvironment. Of note, the plasma levels of crucial inflammatory cytokines are mostly within the normal range in TN patients. Compared to JAK2V617F-mutated patients, the GEP of TN CD34+ cells revealed distinct signatures in key pathways such as survival, cell adhesion, and inflammation. Importantly, we observed the presence of mitochondrial components within plasma EVs and a distinct phenotype in TN-derived EVs compared to the JAK2V617F-mutated MF patients and HD counterparts. Notably, TN EVs promoted the survival of TN CD34+ cells. Along with a specific microRNA signature, the circulating EVs from TN patients are enriched with miR-361-5p. Conclusions Distinct EV-driven signals from the microenvironment are capable to promote the TN malignant hemopoiesis and their further investigation paves the way toward novel therapeutic approaches for rare MF.
Databáze: OpenAIRE
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