Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes (SMD-RMB22)

Impact of the Double Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes Isolated or Not Compared to the Single Haploinsufficiency of RBM22 and Normal Karyotype Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are malignant hematopathies of the elderly characterized by persistent cytopenias and the presence of deregulated clonal hematopoiesis. The risk of progression to acute myeloid leukemia (AML) is variable. Acquired cytogenetic abnormalities are found in less than 50% of de novo cases and up to 80% in secondary MDS. The deletion of the long arm of chromosome 5 (written del(5q)) is the most common abnormality in MDS (15%). Del(5q) MDS has a good prognosis, with a median survival of 6 years and a 15% risk of progression to AML. However, their life expectancy is shorter than the general population, and the quality of life of patients is diminished. These treatments are not that effective over a long period of time or not well tolerated, and the majority of patients die from causes related to their MDS, such as infections (38%), progression to AML (15%), or bleeding (13%). Two genes, RBM22 and SLU7, coding for proteins of the same complex involved in splicing pre-messenger RNA are carried on the long arm of chromosome 5. We investigate the pronostic impact and the predictive value of the double haploinsufficiency of the RBM22 and SLU7 genes in del(5q) myelodysplastic syndromes isolated or not compared to the single haploinsufficiency of RBM22 and normal karyotype myelodysplastic syndromes.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5Q); Myelodysplastic Syndrome With Del(5Q)
• Intervention / Treatment: Genetic: somatic cytogenetic and genetic characterization

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Marie-Bérengère TROADEC; Phone Number: (33)298223324; Email: marie-berengere.troadec@chu-brest.fr
• Study Contact Backup: Name: Nathalie DOUET-GUILBERT; Phone Number: (33)298223324; Email: nathalie.douet-guilbert@chu-brest.fr

Study Locations

• France
  • Brest, France, 29609
    • Recruiting
    • CHRU de Brest
    • Contact: Marie-Bérengère TROADEC
  • Paris, France, 75000
    • Recruiting
    • Groupe Français de cytogénétique Hématologique
    • Contact: Florence Nguyen-Khac
  • Paris, France, 75000
    • Recruiting
    • Groupe Français des Myélodysplasies
    • Contact: Michaela Fontenay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with myelodysplastic syndromes and presenting a deletion of chromosome 5 in their bone marrow cells

Description

Inclusion Criteria:

• Patients diagnosed with del5q MDS isolated or not
• The clinical and biological data are known at the time of diagnosis.
• The clinical and biological data are known 1 year after the diagnosis
• Consent for the collection of samples for research purposes
• Non-opposition obtained

Exclusion Criteria:

• Patients under judicial protection (guardianship, ...)
• Refusal to participate

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
normal karyotype; control group	Genetic: somatic cytogenetic and genetic characterization; investigating the presence of some genes allelles (RBM22, SLU7, RBM27, other on chromosome 5) by FISH, and sequencing of a classical panel of myeloid genes including RBM22, SLU7, for somatic identification of genetic alterationss of the blasts.
del5q-RBM22neg-SLU7neg; this group is characterized by its karyotype. It presents a 5q deletion, a loss of RBM22, a loss of SLU7.	Genetic: somatic cytogenetic and genetic characterization; investigating the presence of some genes allelles (RBM22, SLU7, RBM27, other on chromosome 5) by FISH, and sequencing of a classical panel of myeloid genes including RBM22, SLU7, for somatic identification of genetic alterationss of the blasts.
del5q-RBM22neg-SLU7pos; this group is characterized by its karyotype. It presents a 5q deletion, a loss of RBM22 but no loss of SLU7	Genetic: somatic cytogenetic and genetic characterization; investigating the presence of some genes allelles (RBM22, SLU7, RBM27, other on chromosome 5) by FISH, and sequencing of a classical panel of myeloid genes including RBM22, SLU7, for somatic identification of genetic alterationss of the blasts.
del5q-RBM22pos-SLU7neg; this group is characterized by its karyotype. It presents a 5q deletion, and no loss of RBM22, but a loss in SLU7	Genetic: somatic cytogenetic and genetic characterization; investigating the presence of some genes allelles (RBM22, SLU7, RBM27, other on chromosome 5) by FISH, and sequencing of a classical panel of myeloid genes including RBM22, SLU7, for somatic identification of genetic alterationss of the blasts.
del5q-RBM22pos-SLU7pos; this group is characterized by its karyotype. It presents a 5q deletion, and no loss of RBM22 nor SLU7	Genetic: somatic cytogenetic and genetic characterization; investigating the presence of some genes allelles (RBM22, SLU7, RBM27, other on chromosome 5) by FISH, and sequencing of a classical panel of myeloid genes including RBM22, SLU7, for somatic identification of genetic alterationss of the blasts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prognostic impact on anemia	To evaluate the prognostic impact of the dual loss of an RBM22 and a SLU7 allele compared to the loss of an RBM22 allele alone on anemia, as measured by the hemoglobin level in the blood, between diagnosis and one year in patients with del5q myelodysplastic syndrome.	retrospective study on data collected; 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prognostic impact on blood count	To evaluate the prognostic impact of the double loss of an RBM22 allele and a SLU7 allele compared to the loss of an RBM22 allele alone on the other criteria of the blood count including leukocytes, platelets, monocytes, circulating blasts, VGM, myelemia.	retrospective study on data collected; 2 years
prognostic impact on progression to leukemia	To evaluate the prognostic impact of the double loss of an RBM22 and a SLU7 allele compared to the loss of an RBM22 allele alone on the progression to acute myeloid leukemia.	retrospective study on data collected; 2 years
impact on gene expression and splicing profile	To evaluate the impact of the double loss of an RBM22 allele and a SLU7 allele compared to the loss of an RBM22 allele alone on gene expression profiles, including splicing variants.	retrospective study on RNA collected; 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Principal Investigator: Marie-Bérengère TROADEC, CHRU Brest

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: anemia; RBM22; SLU7; transformation to acute myeloid leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: SMD-RMB22 (29BRC20.0029)

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 beginning three years and ending fifteen years following the publication
• 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