JAK2V617F Mutated Endothelium Has a Stem Cell Potential in Primary Myelofibrosis: a New Disease Ontogenesis for Chronic Myeloproliferative Disorders

NCT07607392 | Completed

• 1 other identifier: RF-2021
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The present project aims to experimentally test the hypothesis that JAK2V617F mutated endothelium in primary myelofibrosis (PMF) we discovered in 2013 represents an embryonic-like hemogenic endothelium and is part of the malignant stem cell pool that give rise to clonal hematopoiesis. The hypothesis stems from the recent evidence that JAK2 mutation in PMF patients is acquired in utero or childhood. The experimental plan of the project is 1) to separate mature endothelial cells from peripheral blood of PMF patients for morphological, molecular, functional characterization and clonogenic assays; 2) to assay the megakaryocyte, erythroid, granulocyte and endothelial clonogenic potential of the mature endothelial cells of patients with PMF. The potential to form colonies will be the documentation that a fraction of mature endothelial cells of patients with PMF have the characteristics of embryonic hemogenic endothelium and might act as the cell of origin of PMF.

Conditions

Primary Myelofibrosids

Keywords

Primary myelofibrosis; Endothelial cells; JAK2V617F mutation

Outcome Measures

Primary Outcomes (3)

• Isolation of endothelial cells

  This will be done by cell sorting of peripheral blood samples from both patients and healthy subjects

  from month 1 to month 18

• Genotyping of sorted endothelial cells

  endothelial cells sorted from patiens or healthy subjects will undergo DNA extraction and assessed for the presence of driver mutations of chronic myeloproliferative diseases

  from month 6 to month 30 of the project

• in vito culture of endothelail cells

  Sorted endothelial cells will be cultured in vitro in a clonogenic assay in order to obtain differentiation into cells opf the hematopoietic lineage, mainly (but not exclusively megakaryocyte)

  from month 6 to month 36 of the project

Study Arms (2)

Patients

Patients affected from primary myelofibrosis

Controls

Healthy subjects whoi volunteer participate to the study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers will be enrolled among people working in the Institutions where the project is conducted (San Matteo Foundation and Pavia University in Pavia and IEO in Milan)

You may qualify if:

• availability to understand and sign the informed consent

You may not qualify if:

• no known concurrent hematologic disease or condition that can affect the interpretation of the results

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead
• University of Pavia: collaborator
• IEO Foundation: collaborator

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, Italy, 27100, Italy

Location

Related Publications (6)

• Di Buduo CA, Laurent PA, Zaninetti C, Lordier L, Soprano PM, Ntai A, Barozzi S, La Spada A, Biunno I, Raslova H, Bussel JB, Kaplan DL, Balduini CL, Pecci A, Balduini A. Miniaturized 3D bone marrow tissue model to assess response to Thrombopoietin-receptor agonists in patients. Elife. 2021 Jun 1;10:e58775. doi: 10.7554/eLife.58775.

  PMID: 34059198 BACKGROUND

• Fadlullah MZH, Neo WH, Lie-A-Ling M, Thambyrajah R, Patel R, Mevel R, Aksoy I, Do Khoa N, Savatier P, Fontenille L, Baker SM, Rattray M, Kouskoff V, Lacaud G. Murine AGM single-cell profiling identifies a continuum of hemogenic endothelium differentiation marked by ACE. Blood. 2022 Jan 20;139(3):343-356. doi: 10.1182/blood.2020007885.

  PMID: 34517413 BACKGROUND

• Farina M, Bernardi S, Polverelli N, D'Adda M, Malagola M, Bosio K, Re F, Almici C, Dunbar A, Levine RL, Russo D. Comparative Mutational Profiling of Hematopoietic Progenitor Cells and Circulating Endothelial Cells (CECs) in Patients with Primary Myelofibrosis. Cells. 2021 Oct 15;10(10):2764. doi: 10.3390/cells10102764.

  PMID: 34685741 BACKGROUND

• Rosti V, Villani L, Riboni R, Poletto V, Bonetti E, Tozzi L, Bergamaschi G, Catarsi P, Dallera E, Novara F, Massa M, Campanelli R, Fois G, Peruzzi B, Lucioni M, Guglielmelli P, Pancrazzi A, Fiandrino G, Zuffardi O, Magrini U, Paulli M, Vannucchi AM, Barosi G; Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative (AGIMM) investigators. Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation. Blood. 2013 Jan 10;121(2):360-8. doi: 10.1182/blood-2012-01-404889. Epub 2012 Nov 5.

  PMID: 23129323 BACKGROUND

• Piaggio G, Rosti V, Corselli M, Bertolotti F, Bergamaschi G, Pozzi S, Imperiale D, Chiavarina B, Bonetti E, Novara F, Sessarego M, Villani L, Garuti A, Massa M, Ghio R, Campanelli R, Bacigalupo A, Pecci A, Viarengo G, Zuffardi O, Frassoni F, Barosi G. Endothelial colony-forming cells from patients with chronic myeloproliferative disorders lack the disease-specific molecular clonality marker. Blood. 2009 Oct 1;114(14):3127-30. doi: 10.1182/blood-2008-12-190991. Epub 2009 Jul 23.

  PMID: 19628707 BACKGROUND

• Zambidis ET, Peault B, Park TS, Bunz F, Civin CI. Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development. Blood. 2005 Aug 1;106(3):860-70. doi: 10.1182/blood-2004-11-4522. Epub 2005 Apr 14.

  PMID: 15831705 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood mononuiclear cells; CD34+ cells, endothelial cells

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Vittorio Rosti

  IRCCS Poiliclinico San Matteo Foundation, Pavia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: May 26, 2026
• Study Start: May 2, 2023
• Primary Completion: February 28, 2026
• Study Completion: April 29, 2026
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)