Clinical Research Directory

MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.

Structural Chromosome Rearrangements and Brain Disorders

The project is focused on the detailed study of structural genomic variants (SVs). Such genetic mutations are in fact alterations in the DNA molecule structure and include copy number variants, inversions and translocations. A single event may affect many genes as well as regulatory regions and the specific phenotypic consequences will depend on the location, genetic content and type of SV. Many times, the specific disease-causing mechanism is not known. Here, the plan is to study the molecular genetic behavior of structural variants as well as the underlying mutational mechanisms involved. First, genome sequencing will be done to pinpoint the chromosomal breakpoints at the nucleotide level, characterize the genomic architecture at the breakpoints and study the relationship between structural variants and SNVs. Second, the aim is to study how structural variants impact gene expression. Finally, disease mechanisms will be functionally explored in vivo using zebrafish and in vitro using primary patient cells and induced pluripotent stem cells. The studies will focus on the origin, structure and impact of structural variation on human disease. The results will directly lead to a higher mutation detection rate in genetic diagnostics. Through a better understanding of disease mechanisms the findings will also assist in the development of novel biomarkers and therapeutic strategies for patients with rare genetic disorders.

Biocollection in MyeloDysplastic Syndrome (P-MDS)

Myelodysplastic syndromes (MDS) are chronic myeloid hemopathies characterized by ineffective hematopoiesis (with peripheral cytopenias) and which contrast with a marrow of normal richness. MDS is considered one of the four most common blood diseases. The incidence is estimated at 4,059 cases / year in 2012 with an average age of 78 years in men and 81 years in women (INCA report, Cancers in France in 2015). The incidence increases with lengthening of the lifespan. The main risk of MDS is transformation to acute leukemia in 30 to 40% of cases. Treatment options depend on clinical, hematologic and chromosomal abnormalities. The prognosis is considered to be at low or high risk of developing acute leukemia. This distinction will therefore have an impact on the therapeutic solution (s). MDS exhibit clinical, morphological and genetic heterogeneity. It is therefore necessary to form subgroups of patients to better understand the physiopathogenesis of this pathology. The constitution of a biocollection will make it possible to search for clinical and biological prognostic markers in order to identify patients progressing to acute myeloid leukemia.