Changes in chromatin structure are observed during aging and are often a critical step during tumorigenesis. The class of long intergenic non-coding RNAs (lincRNA), has emerged as an important regulator of chromatin structure during normal differentiation, and recently has been implicated in the disregulation of chromatin structure observed in several solid tumours. These lincRNAs could represent an important new class of oncogene. We propose to investigate a potential involvement of lincRNAs in chromatin changes that occur during normal aging of haematopoietic stem cells (HSC), and in acute myeloid leukaemia (AML), an age-related haematological malignancy that is frequently associated with chromatin abnormalities. High-throughput sequencing will be used to compare expression of lincRNAs between young and old HSC, and between AML and normal CD34+ cells. Differentially expressed lincRNAs will be functionally investigated by lentiviral-mediated knockdown and overexpression in cell lines and primary cells, and concomitant changes in chromatin structure will be profiled by chromatin immunoprecipitation. It is expected that this project will clarify the general importance of lincRNAs both in normal aging and in an age-related cancer, and could identify novel molecules which are important drivers of malignancy as well as the functional changes associated with HSC aging. As well as being potential prognostic markers and direct targets for therapeutics in AML, these molecules might also be targeted to improve the function of aging HSCs.