Ferroptosis Study in SF3B1-mutant Myelodysplastic Syndromes (FerMDS)

Trial Title: Ferroptosis Study in SF3B1-mutant Myelodysplastic Syndromes (FerMDS)

NCT ID: NCT05924074

Condition: Myelodysplastic Syndromes
Ferroptosis

Conditions: Official terms:
Preleukemia
Myelodysplastic Syndromes
Syndrome

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Diagnostic

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Biological sampling
Description: The procedure will consist of an additional bone marrow sample and blood sample
Arm group label: Monoclonal Gammapathy of Unknown Significance patients (MGUS)
Arm group label: SF3B1 mutant Myelodysplastic syndromes patients (MDS)

Summary: Myelodysplastic syndromes (MDS) are clonal diseases of hematopoietic stem cells (HSC) characterized by dysplastic and inefficient hematopoiesis related to excessive progenitor cell death. Ferroptosis is a recently described cell death mechanism and we think that it could be a major player in the pathophysiology of MDS, involved in the cell death that characterizes these diseases and contributing to cytopenias. The study aims to demonstrate that there is a significant activation of this phenomenon in MDS patients compared to a population of subjects without MDS.

Detailed description: Myelodysplastic syndromes (MDS) are hematological malignancies characterized by a defect in blood cells production. Their pathophysiology remains poorly understood, but an excessive death of progenitor cells is considered as a key mechanism contributing to the appearance of cytopenia. Furthermore, it is known that there are abnormalities of iron metabolism in MDS, especially in patients with ring sideroblasts and SF3B1 mutation. The classical therapeutic strategy in MDS relies on symptomatic management of cytopenias (transfusions, growth factors) associated with demethylating agents in high-risk forms. Unfortunately, these treatments only stabilize the disease and only allogeneic bone marrow transplantation (reserved to limited number of patients) can cure the patients. Therefore, there is a urgent need to identify new therapeutic targets in these diseases. An excessive apoptosis activation has been shown in MDS for a long time. However, other cell death pathways could also contribute to their pathophysiology. Among them, ferroptosis, a cell death process triggered by the accumulation of free iron in the cell, seems to be a promising candidate. The project is proposed to study ferroptosis in SF3B1-mutant MDS patients. An additionnal bone marrow sample will be aspirate at diagnosis. Ferroptosis will be analyzed using flow cytometry (labeling of peroxidized lipids with C11-BODIPY). The percentage of cells in ferroptosis will be compared between SF3B1-mutant MDS patients and control patients (patients evaluated for Monoclonal Gammapathy of Unknown Significance-MGUS). The presence of an excess of ferroptosis in SF3B1-mutant MDS patients will be correlated to clinico-biological parameters. No follow up will be be performed.

Criteria for eligibility:
Criteria:
Inclusion Criteria: For all : - Patients of legal age (age ≥ 18 years) - Subjects affiliated to or benefiting from a social security scheme - Free, written and informed consent signed by the participant and the investigator For MDS patients : - Sampling at diagnosis for MDS patients (WHO 2016 criteria) - Presence of ring sideroblasts on bone marrow smear For MGUS patients : - Sampling as part of the exploration of monoclonal gammopathy of undetermined significance (MGUS) for controls (WHO 2016 criteria). Exclusion Criteria: For all - Patient transfused with red blood cells within 120 days prior to collection - Patients treated with haematopoietic growth factors (EPO, TPO, G-CSF) within 30 days prior to collection - Patients with conditions that affect systemic iron metabolism: hemochromatosis, Gaucher disease, ferroportin disease, porphyria cutanea tarda - Person under a legal protection measure (legal protection, guardianship or curatorship) - Person deprived of liberty by judicial or administrative decision - Person who is unable to give consent - Subject who is in an exclusion period after another study or who has participated in another interventional drug study within 30 days prior to entry into the protocol

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: CHU de Bordeaux, Laboratoire d'Hématologie

Address:
City: Pessac
Country: France

Contact:
Last name: Victor-Emmanuel BRETT
Email: victor.brett@chu-bordeaux.fr

Facility:
Name: CHU de Bordeaux, Service de Médecine Interne

Address:
City: Pessac
Country: France

Contact:
Last name: Estibaliz LAZARO
Email: estibaliz.lazaro@chu-bordeaux.fr

Facility:
Name: CHU de Bordeaux, Service Hématologie Clinique et Thérapie Cellulaire

Address:
City: Pessac
Country: France

Contact:
Last name: Sophie DIMICOLI-SALAZAR
Email: sophie.dimicoli-salazar@chu-bordeaux.fr

Start date: September 2024

Completion date: September 2026

Lead sponsor:
Agency: University Hospital, Bordeaux
Agency class: Other

Source: University Hospital, Bordeaux

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05924074