Oncogenic activation and therapeutic targeting of PIM1 in T-cell acute lymphoblastic lymphoma

T-cell lymphoblastic lymphoma (T-LBL) is an aggressive hematologic malignancy that requires

treatment with intensified chemotherapy. The identification of a PIM1 translocation in a case of

human T-LBL and the notion that PIM1 is overexpressed in a substantial fraction of human T-LBLs

suggests an important oncogenic role for this serine/threonine kinase factor during T-cell

transformation. Nevertheless, the exact molecular mechanism by which PIM1 contributes to the

pathology of this disease remains unclear. In this project, we will identify the genetic mechanisms

that cause aberrant PIM1 activation, define the oncogenic pathways downstream of PIM1 during Tcell

transformation and evaluate PIM1 inhibition as a new therapeutic strategy in human T-cell

lymphoma.