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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Myelodysplastic Syndromes, Myelodysplastic Syndrome With Isolated Del(5Q), Myelodysplastic Syndrome With Del(5Q)

Intervention / Treatment
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* Genetic: somatic cytogenetic and genetic characterization


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| normal karyotype<br>control group | Genetic: somatic cytogenetic and genetic characterization<br>* 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.<br>|
| del5q-RBM22neg-SLU7neg<br>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<br>* 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.<br>|
| del5q-RBM22neg-SLU7pos<br>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<br>* 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.<br>|
| del5q-RBM22pos-SLU7neg<br>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<br>* 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.<br>|
| del5q-RBM22pos-SLU7pos<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RBM22, SLU7, transformation to acute myeloid leukemia, anemia