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Br J Haematol. 2005 Jan;128(1):18-34.

Pathogenesis of acute myeloid leukaemia and inv(16)(p13;q22): a paradigm for understanding leukaemogenesis?

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Molecular Haematology Unit, Division of Molecular and Genetic Medicine, Royal Hallamshire Hospital, Sheffield, UK.


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 CBFbeta-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.

[Indexed for MEDLINE]

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