Project description:Analysis of nucleosome accessibility in CUTLL3 ETP-ALL cells following treatment with Vehicle or Pitavastatin for 48 hours and ETP-ALL patients at diagnosis
Project description:Cell lines representing human T-ALL were analyzed to compare GATA3low ETP-ALL (i.e. PER-117) with "typical" T-ALL. Moreover, changes in global gene expression were assessed comparing GATA3low ETP-ALL (i.e. PER-117) and GATA3high ETP-ALL (i.e. Loucy) upon treatment with Decitabine, a hypomethylating agent. Analysis of 6 human cell lines representing "typical" T-ALL (BE13, Jurkat, Molt4, RPM18402) and ETP-ALL (Loucy, PER-117). Additionally, global gene expression was assessed before and after treatment of ETP-ALL cell lines with Decitabine
Project description:Cell lines representing human T-ALL were analyzed to compare GATA3low ETP-ALL (i.e. PER-117) with "typical" T-ALL. Moreover, changes in global gene expression were assessed comparing GATA3low ETP-ALL (i.e. PER-117) and GATA3high ETP-ALL (i.e. Loucy) upon treatment with Decitabine, a hypomethylating agent.
Project description:Peripheral T cell lymphoma (PTCL) is a very aggressive disease which currently lacks efficient targeted therapy. New therapeutic strategies are needed to improve the very poor outcome of these patients. In these study we hypothesized that PIM kinases could be of therapeutic value in PTCL because we found an overexpression of PIM1 and PIM2, but not PIM3, in PTCL cases, cell lines and primary tumoral T cells from Sezary Syndrome patients, compared with reactive lymph nodes and normal T cells from healthy donors, respectively. In order to understand the mechanism of action of this pan-PIM inhibitor in PTCL, 4 cell lines (DERL7, HuT78, SR786 and MyLa) were treated with 10 μM of ETP-39010 for 0, 2, 4, 6, 10 and 24 h, and gene expression profiling was performed. 4 PTCL cell lines (DERL7, HuT78, SR786 and MyLa) were treated with DMSO and 10 μM of the pan-PIM inhibitor ETP-39010, and hybridized using the Universal Human Reference RNA (Stratagene, La Jolla, CA) as the reference sample.
Project description:Notch1 signaling ramps up to very high levels in order to drive CD4-CD8- double-negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. During this important phase of T-cell development, which is known as the DN-DP transition, it is unclear whether the Notch1 complex simply strengthens its signal output as an isolated unit or recruits cofactors to amplify its signals. We previously showed that the PIAS-like coactivator Zmiz1 is a direct and context-dependent cofactor of Notch1 in T-cell leukemia. Using conditional knockout mouse models, we show that like inactivation of Notch, inactivation of Zmiz1 impaired the DN-DP transition under steady state and stress conditions. To determine mechanism, we performed RNA-Seq on sorted early T-lineage progenitor (ETP) and DN3 cells that were deprived of Zmiz1 signals either acutely (DeltaTamCre) or chronically (DeltaMxCre). To differentiate Notch1-independent from Notch1-dependent target genes, we also performed RNA-Seq on ETP and DN3 cells that were deprived of Notch1 signals using the anti-NRR Notch1 antibody. Our data suggests that Zmiz1 selectively amplifies a subset of Notch1 target genes in DN3 cells, such as Myc. In contrast, Zmiz1 does not have these functions in ETP cells, thus indicating stage-specific roles of Zmiz1.
