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

Myelodysplastic Syndromes Clinical Trial

— SMD-RMB22  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04701229
• Other study ID #: SMD-RMB22 (29BRC20.0029)
• Status: Recruiting
• Start date: September 30, 2020
• Est. completion date: September 30, 2023

Study information

• Verified date: January 2021
• Source: University Hospital, Brest
• Contact: Marie-Bérengère TROADEC
• Phone: (33)298223324
• Email: marie-berengere.troadec[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myelodysplastic Syndrome With Del(5Q)
• Myelodysplastic Syndrome With Isolated Del(5Q)
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
France	CHRU de Brest	Brest
France	Groupe Français de cytogénétique Hématologique	Paris
France	Groupe Français des Myélodysplasies	Paris

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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