The role of LMO4 in T cell acute lymphoblastic leukaemia

The combination of chemotherapy regimens has markedly improved the survival rates of patients suffering with T-cell acute lymphoblastic leukaemia (T-ALL). Nevertheless, there are still patients with poor prognoses, particularly for those experiencing a relapse of the disease. Early T-cell precursor ALL (ETP-ALL) is a subtype of T-ALL with such a poor prognosis and has an immature immunophenotype with a gene expression signature similar to ETPs. The LIM-only 4 (LMO4) protein has recently been found to be overexpressed in this subgroup, where it is supposed to play a critical role in early T-cell development. However, overexpression of other LMO family members such as LMO1 and LMO2 was suggested to displace LMO4 from a DNA-binding complex and thus deregulate the normal T-cell maturation process. To address the role of LMO4 in T-cell maturation we first sought to determine its presence in ETP-ALL cell lines and to identify potential interacting partners that could be present in the same transcriptional complex. We also performed LMO4 gene silencing experiments in order to investigate if it is indeed fundamental for T-cell maturation and survival processes. This research allowed us to characterize two cell lines that can serve as a model for ETP-ALL and provided us with a better insight into the role of the LMO proteins in this type of leukaemia. The presence of LMO4 during ETP maturation process indicates that it could be directly involved during the onset of ETP-ALL.