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

• Conditions: Myelodysplastic Syndrome With Isolated Del(5Q); Myelodysplastic Syndrome With Del(5Q); Myelodysplastic Syndromes
• Interventions: Genetic: somatic cytogenetic and genetic characterization

• Registration Number: NCT04701229
• Lead Sponsor: University Hospital, Brest

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-30
• Status Verified: 2021-01
• Study First Submitted: 2021-01-06
• Study First Submitted QC: 2021-01-06
• Last Update Submitted: 2021-01-06
• Study First Posted: 2021-01-08
• Last Update Posted: 2021-01-08
• Primary Completion: 2022-09-30
• Study Completion: 2023-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
del5q-RBM22pos-SLU7pos	somatic cytogenetic and genetic characterization	this group is characterized by its karyotype. It presents a 5q deletion, and no loss of RBM22 nor SLU7
del5q-RBM22neg-SLU7pos	somatic cytogenetic and genetic characterization	this group is characterized by its karyotype. It presents a 5q deletion, a loss of RBM22 but no loss of SLU7
del5q-RBM22pos-SLU7neg	somatic cytogenetic and genetic characterization	this group is characterized by its karyotype. It presents a 5q deletion, and no loss of RBM22, but a loss in SLU7
normal karyotype	somatic cytogenetic and genetic characterization	control group
del5q-RBM22neg-SLU7neg	somatic cytogenetic and genetic characterization	this group is characterized by its karyotype. It presents a 5q deletion, a loss of RBM22, a loss of SLU7.

Primary Outcome Measures

Name	Time	Method
prognostic impact on anemia	retrospective study on data collected; 2 years	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.

Secondary Outcome Measures

Name	Time	Method
impact on gene expression and splicing profile	retrospective study on RNA collected; 2 years	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.
prognostic impact on blood count	retrospective study on data collected; 2 years	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.
prognostic impact on progression to leukemia	retrospective study on data collected; 2 years	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.

Trial Locations

Locations (3)

CHRU de Brest; 🇫🇷 Brest, France

Groupe Français de cytogénétique Hématologique; 🇫🇷 Paris, France

Groupe Français des Myélodysplasies; 🇫🇷 Paris, France