Project description:Thrombocytopenia is an independent prognostic indicator in patients with MDS (de Swart, L. et al, Br J Haematol, 2015) and we sought to evaluate the contribution of azacitidine to the worsening of this condition in patients with MDS and acute myeloid leukemia (AML). Since MDS/AML may have lower amounts of residual healthy cells, we sought to model this effect of AZA on healthy cord blood derived megakaryocytic cells. We used microarrays to detail the global programme of gene expression in the presence of azacitidine under megakaryocytic differentiation stimulants and identified distinct classes of dysregulated genes and pathways during this process.
Project description:The STOPAGO study enrolled adults with persistent or chronic primary immune thrombocytopenia (ITP) and complete response to thrombopoietin receptor agonist (TPO-RA). TPO-RA discontinuation was planned in the study and patients with sustained complete response off-treatment (SCROT, platelet count > 100 G/L and no bleeding) and non sustained response (NSR, platelet count < 30 G/L or bleeding) were identified at week 24. RNAseq of peripheral blood mononuclear cells was performed at baseline, before TPO-RA discontinuation. Samples originated from 8 patients (4 with SCROT and 4 with NSR). The objectif was to identify putative markers that would predict relapses after TPO-RA discontinuation by comparing SCROT and NSR patients.
Project description:Comprehensive characterization of the DNA methylome regulated by the treatment with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and the relationship of these features with the status of BRG1 and MYC in lung cancer cell lines. MYC amplified cell lines and BRG1 mutant cell lines were treated with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and their methylation was then measured
Project description:TPO mimetics have been shown to activate TPO receptor, the downstream JAK-STAT pathway, and induce differentiation of hematopoietic stem cells into megakaryocytes. However, the action of these TPO mimetics is initiated by binding to the transmembrane domain of the TPO receptor, which is distinct from the binding site of the native ligand, TPO. To determine whether TPO mimetics can differentiate hematopoietic stem cells into the same megakaryocytes as native TPO does, we performed a microarray experiment to compare the globe gene expression in purified CD61+ cells derived from TPO or TPO mimetic treated CD34+ bone marrow cells. Keywords: Drug Treatment
Project description:Comprehensive characterization of the DNA methylome regulated by the treatment with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and the relationship of these features with the status of BRG1 and MYC in lung cancer cell lines.
Project description:To development our gene expression approach , we have employed whole genome microarray expression profiling as a discovery platform to identify genes potentialy regulated by the treatment with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and the relationship of these features with the status of BRG1 and MYC in lung cancer cell lines. MYC amplified cell lines and BRG1 mutant cell lines were treated with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and their expression was then measured
Project description:Small molecular TPO mimetics, LGD-4665 and eltrombopag, were efficacious in stimulating the formation of CD41+ cells from human bone marrow CD34+ cells. To better understand the mechanism of action of TPO mimetics, a microarray study was performed to compare global gene expression in CD34+ cells induced by small molecular TPO mimetics eltrombopag and LGD4665, to changes in response to recombinant human thrombopoietin (TPO). Keywords: Drug Treatment
Project description:To development our gene expression approach , we have employed whole genome microarray expression profiling as a discovery platform to identify genes potentialy regulated by the treatment with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and the relationship of these features with the status of BRG1 and MYC in lung cancer cell lines.