Unraveling the Role of Extracellular Vesicles-driven Senescence in Myeloproliferative Neoplasms

In this study the aim is to investigate the pathogenetic role of extracellular vesicles and senescence in Myeloproliferative Neoplasms. In particular, the goal of this project is to identify possible EV-based biomarkers of senescence according to gender, which are disease-specific, biology-related, and predictive of short-term outcome in terms of Event-Free Survival and to define personalized targets for new therapeutic approaches.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelofibrosis (MF); Polycythemia Vera (PV); Essential Thrombocythemia (ET)

Detailed Description

This is a 3-year multi-centre prospective in vitro study. 120 patients with MPN (ET (n=45), PV (n=45), and MF (n=30)) will be enrolled for a period of 22 months. Follow-up: 12 months. Patients (ET=Group A; PV=Group B; MF=Group C) will be enrolled at the Complex Operative Unit of Haematology-IRCCS Azienda Ospedaliero-Universitaria di Bologna and at the Haematology Centres of Reggio Emilia, Brescia, Meldola, and Ravenna. Peripheral blood samples from patients with ET, PV, and MF (Group A-C; 40 ml) and/or bone marrow samples from patients with ET and PV (Group A, B; 5 ml) will be collected at diagnosis as part of normal clinical practice. The samples will be analysed at the Complex Operative Unit of Haematology-IRCCS Azienda Ospedaliero-Universitaria di Bologna in collaboration with the Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori' - IRST IRCCS (analysis of EV size and concentration) and with the University of Perugia (analysis of EV lipid cargo). The data analysis will be carried out in collaboration with the Department of Physics and Astronomy of the University of Bologna.

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
  • BS
    • Brescia, BS, Italy, 25123
      • Asst Spedali Civili Di Brescia
  • FC
    • Meldola, FC, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori- IRST
  • RA
    • Ravenna, RA, Italy, 48100
      • Ospedale S.Maria delle Croci
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Arcispedale S. Maria Nuova - IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with Myeloproliferative Neoplasms (Essential Thrombocythemia, Polycythemia Vera, Myelofibrosis) will be enrolled over a 28 months period. Follow-up 1 year.

As a control, sex/age matched Healthy Donors will be enrolled among volunteers of a no profit organization called AIL Bologna.

Description

Inclusion criteria for patients:

• age ≥ 18 years.
• patients with WHO2017-defined diagnosis of Myeloproliferative Neoplasms.
• patients at first diagnosis.
• Informed consent signed.

Exclusion criteria for patients:

- patients with concomitant second neoplasia

Inclusion criteria for Healthy Donors:

• age ≥ 18 years.
• Informed consent signed.

Exclusion criteria for Healthy Donors:

- Healthy Donors with neoplasia.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma extracellular vesicle characterization	Comparison of concentration (particles/mL), phenotype, and cargo between extracellular vesicles from patients and healthy donors.	2 years
Validation of extracellular vesicles as biomarker	Correlation of extracellular vesicles' characterization data with markers of disease aggressiveness.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell culture-derived extracellular vesicle characterization	Comparison of the phenotype of extracellular vesicles derived from the supernatant of selected immune cells cultured in the presence or absence of inflammatory factors.	2 years
Extracellular vesicle-mediated senescence	Comparison of senescence biomarkers (such as p16 and p21) in selected immune cells from healthy donors in the presence or absence of extracellular vesicles from patients or healthy donors.	1 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of extracellular vesicles as biomarker	Development of an integrated analysis of clinical data and extracellular vesicle-based scenescence biomarkers to allow the identification of a short-term prognostic index in Myeloproliferative Neoplasm patients.	1 years

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Lucia Catani, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): August 8, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Blood Coagulation Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms; Myeloproliferative Disorders; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: EVs-Sene; FIN-RER_BU_2020_29 (Other Grant/Funding Number: Italian Ministry of Health)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No