Biocollection in MyeloDysplastic Syndrome (P-MDS) (P-MDS)

Biocollection in Patients With Myelodysplastic Syndrome (P-MDS)

Myelodysplastic syndromes (MDS) are chronic myeloid hemopathies characterized by ineffective hematopoiesis (with peripheral cytopenias) and which contrast with a marrow of normal richness. MDS is considered one of the four most common blood diseases. The incidence is estimated at 4,059 cases / year in 2012 with an average age of 78 years in men and 81 years in women (INCA report, Cancers in France in 2015). The incidence increases with lengthening of the lifespan. The main risk of MDS is transformation to acute leukemia in 30 to 40% of cases. Treatment options depend on clinical, hematologic and chromosomal abnormalities. The prognosis is considered to be at low or high risk of developing acute leukemia. This distinction will therefore have an impact on the therapeutic solution (s). MDS exhibit clinical, morphological and genetic heterogeneity. It is therefore necessary to form subgroups of patients to better understand the physiopathogenesis of this pathology. The constitution of a biocollection will make it possible to search for clinical and biological prognostic markers in order to identify patients progressing to acute myeloid leukemia.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Chromosome Abnormality; Acute Myeloid Leukemia With Multilineage Dysplasia; Myelodysplastic Syndrome With Ring Sideroblasts; Myelodysplastic Anemia; Myelodysplastic Syndrome With Isolated Del(5Q)
• Intervention / Treatment: Other: description of MDS pzatient cohort

Detailed Description

The objective of the biocollection is to respond to 3 scientific projects in MDS :

Project 1: splicing anomalies in MDS with SF3B1 mutations : About 95% of the coding genes in humans are subjected to alternative splicing, a complex, highly regulated mechanism that diversifies the proteome by defining multiple proteins from a single gene. Deregulation of splicing is observed in many cancers and hemopathies (review Yoshida et al., 2014), especially in myelodysplastic syndromes More than half of MDS patients present an acquired mutation in a gene involved in the splicing of pre -RNA messengers. The SF3B1 gene (splice factor 3B subunit 1), which encodes a protein involved in the recognition of 3 'splice sites is the most frequently mutated gene in SMDs, at a frequency of 20-28% MDS, and up to 85% of myelodysplastic syndromes with crowned sideroblasts (Yoshida et al., 2011, Papaemmanuil et al., 2011). The functional consequences of the splicing abnormalities thus generated on the pathophysiology of MDS are far from clear. The transcriptome analyzes (by RNA-seq) carried out recently in various acquired pathologies that the most frequent variants of the SF3B1 gene lead to the formation of aberrant transcripts by the use of a 3 ' cryptic splicing site. The investigators seek to study the functional implications of SF3B1 mutations found in MDS patients in particular on the formation of sideroblasts in the crown. The investigators want to identify, by RNAseq, the aberrant junctions specifically expressed in the cells of MDS patients with mutated SF3B1, and which would affect transcripts of genes involved in iron metabolism or its regulation. For this, the investigators will use the cells obtained from the marrow of SMD SF3B1WT patients versus SF3B1K700E and collected in the Chromosomal Genetics laboratory, site of the CRB of the CHRU of Brest. The investigators will then analyze the functional repercussions associated with the presence of these aberrant junctions on the cells in culture of these same patients (detection of certain proteins, enzymatic analyzes, etc.). The collection of biological and clinical data from these patients of interest is essential for the interpretation of the results. This project is part of a more global approach to the study of the various splicing anomalies in this pathology.

Project 2: splicing abnormalities in MDS with chromosomal abnormalities as 5q deletion : Chromosome 5 deletions are the most frequent structural abnormalities in MDS and constitute a good prognostic entity if isolated or associated with an anomaly and poor prognosis if associated with more than 3 chromosomal abnormalities. Two genes located on chromosomes 5 encode proteins of a complex involved in the splicing of pre-messenger RNAs: the RBM22 gene (RNA Binding Motif Protein 22) and the SLU7 gene (SLU7 Homolog Splicing Factor).

The investigators want to identify subgroups of patients with loss of these 2 genes or loss of RBM22 and conservation of SLU7. Does the loss of one or both genes play a role in the pathophysiogenesis of MDS with chromosome deletions and is it associated with worsening of the disease? Understanding these mechanisms could also have an impact on the therapeutic management of this pathology.

The study of these chromosomal abnormalities associated with splicing abnormalities in MDS for the chromosomal genetics laboratory both from a diagnostic and research perspective. Several works carried out have given rise to numerous scientific publications with an international reading committee for several years.

Project 3: Evolution of MDS in acute myeloid leukemia (AML) More than one third of patients with MDS progress to AML. The investigators want to focus on this group of patients and understand the clonal architecture of their malignant cells to detect new predictive markers of indolent or rapid disease progression.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathalie Douet-Guilbert, MD, PhD; Phone Number: +33229020215; Email: nathalie.douet-guilbert@chu-brest.fr
• Study Contact Backup: Name: Marie-Bérengère Troadec, PhD; Phone Number: +33229020215; Email: marie-berenger.troadec@chu-brest.fr

Study Locations

• France
  • Brest, France, 29609
    • Recruiting
    • CHU Brest
    • Contact: Nathalie DOUET-GUILBERT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Major
• patient with or suspected of myelodysplastic syndrome (WHO definition) at diagnosis and/or during follow-up, which is managed at the level of the Cancer-Hematology Institute of the Brest CHRU
• Presence of biological material collected within the CRB
• Patient's consent obtained

Exclusion Criteria :

• Minor and pregnant woman
• Lack of biological material collected within the CRB
• Refusal to participate: lack of consent - Unable to consent
• Patient under judicial protection: guardianship, curatorship ...

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: MDS follow up; it is a description MDS patients study	Other: description of MDS pzatient cohort; description of MDS patient cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort MDS: epidemiologic MSD study	MDS study in collecting data	five years

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Principal Investigator: Nathalie Douet-Guilbert, MD,PhD, CHRU Brest

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2022
• Primary Completion (Estimated): October 19, 2032
• Study Completion (Estimated): October 19, 2032

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: AML; MDS; 5q deletion; ring sideroblasts
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Genetic Diseases, Inborn; Disease; Hematologic Diseases; Precancerous Conditions; Congenital Abnormalities; Bone Marrow Diseases; Syndrome; Preleukemia; Myelodysplastic Syndromes; Chromosome Disorders; Chromosome Aberrations
• Other Study ID Numbers: 29BRC20.0228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No