Raboso-Gallego Javier, Casado-García Ana, Isidro-Hernández Marta, Vicente-Dueñas Carolina
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Salamanca, Spain.
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
Front Cell Dev Biol. 2019 Jul 17;7:137. doi: 10.3389/fcell.2019.00137. eCollection 2019.
Leukemogenesis is considered to be a process by which a normal cell acquires new but aberrant identity in order to disseminate a malignant clonal population. Under this setting, the phenotype of the leukemic cells is identical to the leukemia-initiating cell in which the genetic insult is taking place. Thus, with some exceptions, B-cell and T-cell childhood leukemias are supposed to arise from B- or T-committed cells. In contrast, several recent studies have revealed that genetic alterations may act in a "hit-and-run" way in the cell-of-origin by imposing the tumor cell identity giving rise to either B-cell or T-cell leukemias. This novel mechanism of cell transformation is mediated by an epigenetic priming mechanism that is established by the initial genetic lesion. This initial hit might be unnecessary for the subsequent tumor evolution and conservation, being the epigenetic priming the engine for the tumor evolution.
白血病发生被认为是一个正常细胞获得新的但异常特性以播散恶性克隆群体的过程。在这种情况下，白血病细胞的表型与发生基因损伤的白血病起始细胞相同。因此，除了一些例外情况，儿童B细胞和T细胞白血病被认为起源于B或T定向细胞。相比之下，最近的几项研究表明，基因改变可能以“打了就跑”的方式在起源细胞中起作用，通过赋予肿瘤细胞特性从而引发B细胞或T细胞白血病。这种新的细胞转化机制由最初的基因损伤建立的表观遗传启动机制介导。这种最初的打击对于随后的肿瘤进展和维持可能并非必要，表观遗传启动才是肿瘤进展的驱动力。
