9 research outputs found
Mise au point d'une technique de détection des autoanticorps anti-signal recognition particule (SRP)
LYON1-BU Santé (693882101) / SudocSudocFranceF
Design, synthesis, and evaluation of triazole derivatives that induce Nrf2 dependent gene products and inhibit the Keap1-Nrf2 protein-protein interaction
The transcription factor Nrf2 regulates
the expression of a large
network of cytoprotective and metabolic enzymes and proteins. Compounds
that directly and reversibly inhibit the interaction between Nrf2
and its main negative regulator Keap1 are potential pharmacological
agents for a range of disease types including neurodegenerative conditions
and cancer. We describe the development of a series of 1,4-diphenyl-1,2,3-triazole
compounds that inhibit the Nrf2–Keap1 protein–protein
interaction (PPI) in vitro and in live
cells and up-regulate the expression of Nrf2-dependent gene products
Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models
Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease generally associated with poor prognosis. Gene expression profiles indicate the existence of distinct molecular subgroups, and several genetic alterations have been characterized in the past years, including the t(1;22)(p13;q13) and the trisomy 21 associated with GATA1 mutations. However, the majority of patients do not present with known mutations, and the limited access to primary patient leukemic cells impedes the efficient development of novel therapeutic strategies. In this study, using a xenotransplantation approach, we have modeled human pediatric AMKL in immunodeficient mice. Analysis of high-throughput RNA sequencing identified recurrent fusion genes defining new molecular subgroups. One subgroup of patients presented with MLL or NUP98 fusion genes leading to up-regulation of the HOX A cluster genes. A novel CBFA2T3-GLIS2 fusion gene resulting from a cryptic inversion of chromosome 16 was identified in another subgroup of 31% of non-Down syndrome AMKL and strongly associated with a gene expression signature of Hedgehog pathway activation. These molecular data provide useful markers for the diagnosis and follow up of patients. Finally, we show that AMKL xenograft models constitute a relevant in vivo preclinical screening platform to validate the efficacy of novel therapies such as Aurora A kinase inhibitors