Even if its completed form is complex, cancer originates from one or two events that happened to a single cell. A simplified model can play a role in understanding how cancer initiates at the beginning. The pathophysiology of leukemia has been studied in the most detailed manner among all human cancers. In this review, based on milestone papers and the latest research developments in hematology, acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML), and acute myeloid leukemia (AML) with RUNX1-RUNX1T1 are selected to consider minimal requirements for cancer initiation. A one-hit model can be applied to the initiation of APL and CML whereas a two-hit model is more suitable to the initiation of AML with RUNX1-RUNX1T1 and other AMLs. Even in cancer cells with multiple genetic abnormalities, there must be a few mutant genes critical for the mutant clone to survive and proliferate. Such genes should be identified and characterized in each case in order to develop individualized target therapy.
即使其最终形态复杂，癌症起源于单个细胞发生的一到两个关键事件。简化模型有助于理解癌症的初始发生机制。在所有人类癌症中，白血病的病理生理学研究最为深入。本文基于血液学领域的里程碑式文献及最新研究进展，选取急性早幼粒细胞白血病（APL）、慢性粒细胞白血病（CML）及伴RUNX1-RUNX1T1融合基因的急性髓系白血病（AML）作为研究对象，探讨癌症发生的最低必要条件。APL和CML的发生符合"单次打击"模型，而伴RUNX1-RUNX1T1融合基因的AML及其他类型AML更适用于"二次打击"模型。即使在具有多重基因异常的癌细胞中，也必然存在少数对突变克隆存活增殖至关重要的基因。针对每个病例识别并解析此类基因特征，将为实现个体化靶向治疗奠定基础。
肿瘤(癌症)患者之家