Resumen de Cancer induction by restriction of oncogene expression to the stem cell compartment

Maria Perez, César Cobaleda Hernández, Inés González Herrero, Carolina Vicente Dueñas, Camino Bermejo Rodríguez, Margarita Sánchez Beato Gómez, Alberto Orfao, Belén Pintado Sanjuanbenito, Teresa Flores Ruano, Manuel Sánchez Martín, Rafael Jiménez Fernández, Miguel Ángel Piris Pinilla, Isidro Sánchez García

• In human cancers, all cancerous cells carry the oncogenic genetic lesions. However, to elucidate whether cancer is a stem cell-driven tissue, we have developed a strategy to limit oncogene expression to the stem cell compartment in a transgenic mouse setting. Here, we focus on the effects of the BCR-ABLp210 oncogene, associated with chronic myeloid leukaemia (CML) in humans. We show that CML phenotype and biology can be established in mice by restricting BCR-ABLp210 expression to stem cell antigen 1 (Sca1)+ cells. The course of the disease in Sca1-BCR-ABLp210 mice was not modified on STI571 treatment. However, BCR-ABLp210-induced CML is reversible through the unique elimination of the cancer stem cells (CSCs). Overall, our data show that oncogene expression in Sca1+ cells is all that is required to fully reprogramme it, giving rise to a full-blown, oncogene-specified tumour with all its mature cellular diversity, and that elimination of the CSCs is enough to eradicate the whole tumour.