Biocollection in MyeloDysplastic Syndrome (P-MDS)

The objective of the biocollection is to respond to 3 scientific projects in MDS :

Project 1: splicing anomalies in MDS with SF3B1 mutations : About 95% of the coding genes in humans are subjected to alternative splicing, a complex, highly regulated mechanism that diversifies the proteome by defining multiple proteins from a single gene. Deregulation of splicing is observed in many cancers and hemopathies (review Yoshida et al., 2014), especially in myelodysplastic syndromes More than half of MDS patients present an acquired mutation in a gene involved in the splicing of pre -RNA messengers. The SF3B1 gene (splice factor 3B subunit 1), which encodes a protein involved in the recognition of 3 'splice sites is the most frequently mutated gene in SMDs, at a frequency of 20-28% MDS, and up to 85% of myelodysplastic syndromes with crowned sideroblasts (Yoshida et al., 2011, Papaemmanuil et al., 2011). The functional consequences of the splicing abnormalities thus generated on the pathophysiology of MDS are far from clear. The transcriptome analyzes (by RNA-seq) carried out recently in various acquired pathologies that the most frequent variants of the SF3B1 gene lead to the formation of aberrant transcripts by the use of a 3 ' cryptic splicing site. The investigators seek to study the functional implications of SF3B1 mutations found in MDS patients in particular on the formation of sideroblasts in the crown. The investigators want to identify, by RNAseq, the aberrant junctions specifically expressed in the cells of MDS patients with mutated SF3B1, and which would affect transcripts of genes involved in iron metabolism or its regulation. For this, the investigators will use the cells obtained from the marrow of SMD SF3B1WT patients versus SF3B1K700E and collected in the Chromosomal Genetics laboratory, site of the CRB of the CHRU of Brest. The investigators will then analyze the functional repercussions associated with the presence of these aberrant junctions on the cells in culture of these same patients (detection of certain proteins, enzymatic analyzes, etc.). The collection of biological and clinical data from these patients of interest is essential for the interpretation of the results. This project is part of a more global approach to the study of the various splicing anomalies in this pathology.

Project 2: splicing abnormalities in MDS with chromosomal abnormalities as 5q deletion : Chromosome 5 deletions are the most frequent structural abnormalities in MDS and constitute a good prognostic entity if isolated or associated with an anomaly and poor prognosis if associated with more than 3 chromosomal abnormalities. Two genes located on chromosomes 5 encode proteins of a complex involved in the splicing of pre-messenger RNAs: the RBM22 gene (RNA Binding Motif Protein 22) and the SLU7 gene (SLU7 Homolog Splicing Factor).

The investigators want to identify subgroups of patients with loss of these 2 genes or loss of RBM22 and conservation of SLU7. Does the loss of one or both genes play a role in the pathophysiogenesis of MDS with chromosome deletions and is it associated with worsening of the disease? Understanding these mechanisms could also have an impact on the therapeutic management of this pathology.

The study of these chromosomal abnormalities associated with splicing abnormalities in MDS for the chromosomal genetics laboratory both from a diagnostic and research perspective. Several works carried out have given rise to numerous scientific publications with an international reading committee for several years.

Project 3: Evolution of MDS in acute myeloid leukemia (AML) More than one third of patients with MDS progress to AML. The investigators want to focus on this group of patients and understand the clonal architecture of their malignant cells to detect new predictive markers of indolent or rapid disease progression.