T-cell leukemogenesis is an inappropriate lineage decision-making process: implications for precision oncology

Abstract

Genetic lineage tracing in cell type-specific mouse models of T-cell acute lymphoblastic leukemia (T-ALL) have revealed that tumor cell identity is imposed by expression of the oncogene Lim Domain Only 2 (LMO2), rather than by the target cell phenotype. This approach allowed to identify that secondary genomic alterations, like Notch1 mutations, appeared late and only took place within the thymus during T-ALL development. These concepts are therefore critical for the development of modern therapies aimed at curing T-ALL.

Keywords

• lmo2
• notch1
• stem cells
• cancer
• mouse models
• target cell
• cancer cell-of-origin
• cancer-stem-cell and tumor reprogramming