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

Sponsor

University Hospital, Brest (Other)

Overall Status

Recruiting

CT.gov ID

NCT04701229

Collaborator

(none)

100

Enrollment

Locations

Anticipated Duration (Months)

33.3

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes Myelodysplastic Syndrome With Isolated Del(5Q) Myelodysplastic Syndrome With Del(5Q)	Genetic: somatic cytogenetic and genetic characterization

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

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.

Actual Study Start Date :

Sep 30, 2020

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	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.

Outcome Measures

Primary Outcome Measures

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

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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHRU de Brest	Brest	France	29609
2	Groupe Français de cytogénétique Hématologique	Paris	France	75000
3	Groupe Français des Myélodysplasies	Paris	France	75000