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By Stanley Shostak (Ed.)

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2007). Once Pax5 expression has been initiated, progenitors lose their potential and are only able to differentiate along a unidirectional path towards mature B cells. , 1994) B cell development cannot progress beyond the pro-B cell stage. However, since they are not yet committed, Pax5-/- proB cells behave as multipotent progenitors, because they express multilineage genes (that would have been otherwise repressed by Pax5 in normal conditions), and this allows them to be programmed into most of the haematopoietic lineages under the right conditions.

Cancer was not so prevalent in ancient times, since life span was much shorter, but it was already clearly identified. Hippocrates (460–375 BC) noted that growing tumors occurred mostly in adults and they reminded him of a moving crab, which led to the terms carcinos and cancer. Celsus (25 BC–AD 50) also compared cancer with a crab, because it adheres to surrounding structures like if it had claws; he introduced the first classification for breast carcinoma and recommended surgical therapy. However, he already noted that tumors could only be cured if removed at early stages because, even after excision and correct healing of the scar, breast carcinomas could recur with swelling in the armpit and cause death by spreading into the body.

This indicates a pathological direct reprogramming mediated by the oncogenic lesions. The other alternative is that of the cancer cell-of-origin being a differentiated cell type. In this case the cells must be reprogrammed not only towards a new fate, but also to regain stem cell characteristics in a process of tumoral reprogramming to pluripotency. For this to occur, two aspects have to come together: first, the oncogenic alteration must be capable of conferring the stem properties and, second, the cell must have a degree of plasticity that allows the reprogramming mediated for this specific alteration to take place.

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