Role of Myeloid-derived Suppressor Cells In Primary Myelofibrosis

NCT07319026 | Completed

• 1 other identifier: 2023-3.11/207
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this observational study are to investigate the role of myeloid-derived suppressor cells (MDSCs) in fueling chronic inflammation that is a relevant pathogenetic mechanism in patients with primary myelofibrosis (PMF), to study modifications in MDSC phenotype and function after treatment with JAK-inhibitors (JAK-i) and to test their participation in the neoangiogenic process. The main questions it aims to answer are:

• Do the frequency and function of MDSCs contribute to induce or sustain the inflammatory status that characterizes PMF?
• Does the number of circulating MDSCs in PMF patients correlate with clinical/biological parameters?
• Are MDSCs involved in the neoangiogenic processes that characterizes PMF?

Conditions

Primary Myelofibrosis (PMF); Healthy Subjects

Keywords

primary myelofibrosis; inflammation; myeloid derived suppressor cells

Outcome Measures

Primary Outcomes (2)

• Percentage of circulating MDSCs

  Freshly obtained PB mononuclear cells will be stained with a cocktail of 4 monoclonal antibodies, acquired on a flow cytometer and analyzed with the gating strategy set up in different papers to identify the two principal subsets of MDSCs (PMN-MDSCs and M-MDSCs). In these cells the investigators will evaluate pSTAT3, together with the ROS intracellular levels that will be detected using a commercially available kit. For all the experiments, 2x10e6 cells will be acquired on a flow cytometer FACS Canto II and analyzed using FACSDivaTM. The number of PMN-MDSCs and M-MDSCs will be calculated as percentage of the total number of acquired cells.

  From the first enrollment through study completion, an average of 1 year

• Correlations between MDSC and clinical/genetic parameters

  Demographic, clinical and laboratory data of PMF patients will be correlated with the percentage of circulating MDSCs.The appropriate multivariate analysis, with both categorical and continuous covariates, will be used to analyze the difference between groups. STATISTICA software (StatSoft) will be used for all statistical analyses and a P value \<0.05 is considered statistically significant.

  From the first enrollment through study completion, an average of 1 year

Secondary Outcomes (2)

• Number of MDSCs in splenic tissue samples

  From the first enrollment through study completion, an average of 1 year

• Plasmatic levels of cytokines and chemokines

  From the first enrollment through study completion, an average of 1 year

Study Arms (2)

Patients with primary myelofibrosis (PMF)

Patients with primary myelofibrosis, diagnosed according to the revised 2016 WHO classification, were enrolled at the Center for the Study of Myelofibrosis. Participants will undergo blood sampling only once during a routine visit.

Healthy subjects

Healthy individuals participating to this study will be selected among regular blood donors at Fondazione IRCCS San Matteo. Blood samples will be taken during a blood donation.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The participants will be recruited at the Center for the Study of Myelofibrosis, Fondazione IRCCS Policlinico San Matteo, Pavia through referring physician.

You may qualify if:

• age \>18 years;
• diagnosis of primary myelofibrosis according to 2016 WHO criteria;
• willing to participate and understanding and signing the I.C.

You may not qualify if:

• concurrent or recent diagnosis of an inflammatory disease and/or neoplasia;
• any other condition that can confounds the ability to interpret data from the study;
• concurrent pregnancy. No vulnerable participants will be enrolled in the study.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, Italy, 27100, Italy

Location

Related Publications (8)

• Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol. 2020 Oct;191(2):152-170. doi: 10.1111/bjh.16576. Epub 2020 Mar 20.

  PMID: 32196650 BACKGROUND

• Hasselbalch HC, Bjorn ME. MPNs as Inflammatory Diseases: The Evidence, Consequences, and Perspectives. Mediators Inflamm. 2015;2015:102476. doi: 10.1155/2015/102476. Epub 2015 Oct 28.

  PMID: 26604428 BACKGROUND

• Koschmieder S, Chatain N. Role of inflammation in the biology of myeloproliferative neoplasms. Blood Rev. 2020 Jul;42:100711. doi: 10.1016/j.blre.2020.100711. Epub 2020 May 30.

  PMID: 32505517 BACKGROUND

• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009 Mar;9(3):162-74. doi: 10.1038/nri2506.

  PMID: 19197294 BACKGROUND

• Consonni FM, Porta C, Marino A, Pandolfo C, Mola S, Bleve A, Sica A. Myeloid-Derived Suppressor Cells: Ductile Targets in Disease. Front Immunol. 2019 May 3;10:949. doi: 10.3389/fimmu.2019.00949. eCollection 2019.

  PMID: 31130949 BACKGROUND

• Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008 Aug;8(8):618-31. doi: 10.1038/nrc2444. Epub 2008 Jul 17.

  PMID: 18633355 BACKGROUND

• Wang JC, Kundra A, Andrei M, Baptiste S, Chen C, Wong C, Sindhu H. Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm. Leuk Res. 2016 Apr;43:39-43. doi: 10.1016/j.leukres.2016.02.004. Epub 2016 Feb 16.

  PMID: 26943702 BACKGROUND

• Campanelli R, Carolei A, Catarsi P, Abba C, Boveri E, Paulli M, Gentile R, Morosini M, Albertini R, Mantovani S, Massa M, Barosi G, Rosti V. Circulating Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSCs) Have a Biological Role in Patients with Primary Myelofibrosis. Cancers (Basel). 2024 Jul 16;16(14):2556. doi: 10.3390/cancers16142556.

  PMID: 39061196 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

* spleen tissue samples (embedded in OCT compound and snap-frozen in liquid nitrogen) * plasma samples (stored at -80°C)

MeSH Terms

Conditions

Primary Myelofibrosis; Inflammation

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: January 6, 2026
• Study Start: November 14, 2023
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: January 6, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)