T-cell acute lymphoblastic leukaemia (T-ALL) is a disease characterized by the uncontrolled clonal proliferation of immature lymphoid cells. Despite improvement in remission rates using conventional chemotherapeutics, the prognosis for T-ALL remains poor due to disease relapse associated with intrinsic, or acquired tumor cell resistance to the initial therapies. Although T-ALL is a genetically heterogenous disease, mutations resulting in activation of the Notch-1 signaling pathway are present in over 50% of patients, thus defining Notch signaling as a central player in T-ALL onset and progression. Studies also defined an oncogenic c-MYC gene signature as a key characteristic of these T-ALL and connectivity map experiments implicated histone deacetylase inhibitors (HDACi) as potential modifiers of pathways de-regulated by Notch. Recently, studies have shown that panobinostat, an FDA-approved HDACi shows efficacy against human T-ALL cell lines in-vitro, but the molecular mechanism that underpin the therapeutic efficacy of panobinostat is poorly understood. To investigate this, we performed 3'mRNA-seq analysis on T-ALL cells treated for 2 hours with panobinostat in vitro. SOURCE: Stephin,J,Vervoort (stephin.vervoort@petermac.org) -  Peter MacCallum Cancer Centre

Pluto Bioinformatics

GSE102757: Comparison of gene expression between control and Panobinostat treated Notch1-driven T-ALL