Pathogenesis of acute myeloid leukaemia and inv(16)(p13;q22): a paradigm for understanding leukaemogenesis?
Pathogenesis of acute myeloid leukaemia and inv(16)(p13;q22): a paradigm for understanding leukaemogenesis?
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DOI：
10.1111/j.1365-2141.2004.05236.x
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发表时间：
2005-01
影响因子：
6.5
通讯作者：
J. Reilly
中科院分区：
文献类型：
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作者：
J. Reilly
急性髓性白血病（AML）被认为是由两类突变（I类或增殖性突变和II类或阻断性突变）之间的协同作用引起的。这种所谓的“两次打击”假设的局限性是在大多数AML病例中缺乏可识别的增殖和阻断突变。然而，现在已知AML和inv中的CBFβ-MYH 11融合基因通过破坏核心结合因子（CBF）的正常转录因子活性而发挥II类突变的功能（16）。此外，已知近70%的AML和inv患者（16）具有受体酪氨酸激酶（RTK）、c-KIT和FLT 3以及RAS基因的互斥突变，这些突变提供I类或增殖性信号。因此，AML和inv（16）是在遗传水平上对急性白血病最好的理解之一，因此为白血病发生的“两次打击”假说提供了范例。本文综述了AML和inv分子病理学的最新进展，并讨论了当前发病模型的可能治疗意义。
Acute myeloid leukaemia (AML) has been proposed to arise from the collaboration between two classes of mutation, a class I, or proliferative, mutation and a class II, or blocking, mutation. A limitation of this so‐called ‘two‐hit’ hypothesis has been the lack of identifiable proliferative and blocking mutations in most AML cases. However, it is now known that the CBFβ–MYH11 fusion gene in AML and inv(16), by disrupting the normal transcription factor activity of core binding factor (CBF), functions as a class II mutation. In addition, nearly 70% of patients with AML and inv(16) are known to possess mutually exclusive mutations of the receptor tyrosine kinases (RTKs), c‐KIT and FLT3, as well as RAS genes, that provide a class I, or proliferative, signal. AML and inv(16), therefore, is one of the best understood of the acute leukaemias at the genetic level and so provides a paradigm for the ‘two‐hit’ hypothesis of leukaemogenesis. This paper reviews the recent advances in the molecular pathology of AML and inv(16) and discusses possible therapeutic implications of the current pathogenetic model.