INSERM, U, Villejuif, France.
Cancer Cell. 2011 Jul 12;20(1):25-38. doi: 10.1016/j.ccr.2011.06.003. Epub 2011 Jun 30.
Loss-of-function mutations affecting one or both copies of the Ten-Eleven-translocation (TET)2 gene have been described in various human myeloid malignancies. We report that inactivation of Tet2 in mouse perturbs both early and late steps of hematopoiesis including myeloid and lymphoid differentiation in a cell-autonomous manner, endows the cells with competitive advantage, and eventually leads to the development of malignancies. We subsequently observed TET2 mutations in human lymphoid disorders. TET2 mutations could be detected in immature progenitors endowed with myeloid colony-forming potential. Our results show that the mutations present in lymphoid tumor cells may occur at both early and later steps of lymphoid development and indicate that impairment of TET2 function or/and expression predisposes to the development of hematological malignancies.
功能丧失性突变影响 Ten-Eleven-translocation（TET）2 基因的一个或两个拷贝已在各种人类髓系恶性肿瘤中被描述。我们报告称，Tet2 在小鼠中的失活以细胞自主性方式扰乱了造血的早期和晚期步骤，包括髓系和淋巴系分化，赋予细胞竞争优势，并最终导致恶性肿瘤的发展。随后，我们在人类淋巴系统疾病中观察到了 TET2 突变。TET2 突变可在具有髓系集落形成潜力的未成熟祖细胞中检测到。我们的结果表明，淋巴肿瘤细胞中的突变可能发生在淋巴发育的早期和晚期阶段，并表明 TET2 功能或/和表达的损伤易导致血液系统恶性肿瘤的发展。
