Histone H3 lysine 27 acetylation (H3K27ac) profile of primary CLL cells transduced with a retrovirus expressing mutated NOTCH1

In chronic lymphocytic leukemia (CLL), NOTCH1 is the most commonly mutated gene at diagnosis and it is associated with a poor outcome. The mechanisms underlying how NOTCH1 contributes to disease progression, resistance to treatment and Richter's transformation remain largely unknown. The main goal of this study is to compare the chromatin activation profile of primary CLL cells transduced with the intracellular part of NOTCH1 lacking of the PEST domain vs. cells transduced with an empty vector. Additionally, patients with the Trisomy 12 abnormality are included in this study to clarify the role of the mutations in this specific sub-group of CLL patients that are strongly associated with NOTCH1 mutations. Overall design: Primary CLL cells from 5 patients were isolated through cell sorting 4 days post transduction with a NOTCH1?PEST or an empty retroviral vector. Patients P1 and P4 have the Trisomy 12 abnormality.