Myelodysplastic Syndromes, Myelodysplastic Syndrome With Del(5Q), Myelodysplastic Syndrome With Isolated Del(5Q)
Conditions
Keywords
RBM22, SLU7, transformation to acute myeloid leukemia, anemia
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.
Interventions
GENETICsomatic 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.
Sponsors
University Hospital, Brest
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France
Contacts
Primary ContactMarie-Bérengère TROADEC
Backup ContactNathalie DOUET-GUILBERT
Outcome results
None listed