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Two cell lines of t(8;21) acute myeloid leukemia with activating KIT exon 17 mutation: models for the ‘second hit’ hypothesis

Leukemia volume 22, pages 1792–1794 (2008)Cite this article

In up to 30% of acute myeloid leukemia (AML), chromosomal translocations disrupt one of the core binding factor (CBF) genes most frequently by the t(8;21)(q22;q22). Although patients with CBF leukemia generally have a higher complete remission rate and disease-free survival as compared to those with a normal karyotype or other chromosomal aberrations, additional distinct mutations in genes involved in signal-transduction pathways, particularly in receptor tyrosine kinases (RTKs), herald a higher relapse rate (see below).

The 2-hit hypothesis proposes that most acute leukemias are the consequence of a collaboration of several types of mutations.1 Class I mutations often affect genes of RTKs, which confer a proliferative and survival advantage to hematopoietic progenitors. Class II mutations are usually chromosomal translocations involving hematopoietic transcription factors, with consecutive impairment of differentiation and apoptosis of cells. Mouse models with high transgene expression of the fusion protein AML1/ETO do not develop leukemia spontaneously.2 In contrast, specific additional mutational events, for example, FLT3 length mutations, can promote development of leukemia in an AML1/ETO mouse model.3 There is evidence in cells haploinsufficient for AML1 suggesting a similar cooperative role for the RTK c-kit.4

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Acknowledgements

This work was supported in part by the German José-Carreras Foundation (R 06/40f).

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Authors and Affiliations

  1. Department for Hematology and Oncology, University Medical Center, Freiburg, Germany

    H Becker, D Pfeifer, J D Afonso, H Veelken, M Schwabe & M Lübbert

  2. Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    S D Nimer

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  1. H Becker
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Correspondence to M Lübbert.

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Becker, H., Pfeifer, D., Afonso, J. et al. Two cell lines of t(8;21) acute myeloid leukemia with activating KIT exon 17 mutation: models for the ‘second hit’ hypothesis. Leukemia 22, 1792–1794 (2008). https://doi.org/10.1038/leu.2008.61

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