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Acute Non-Lymphocytic Leukemias

Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22)

Leukemia volume 19, pages 1361–1366 (2005)Cite this article

Abstract

AML1-MTG8 generated by t(8;21) contributes to leukemic transformation, but additional events are required for full leukemogenesis. We examined whether mutations in the receptor tyrosine kinase (RTK) pathway could be the genetic events that cause acute myeloblastic leukemia (AML) harboring t(8;21). Mutations in the second tyrosine kinase domain, juxtamembrane (JM) domain and exon 8 of the C-KIT gene were observed in 10, one and three of 37 AML patients with t(8;21), respectively. Three patients showed an internal tandem duplication in the JM domain of the FLT3 gene. One patient had a mutation in the K-Ras gene at codon 12. As the occurrence of these mutations was mutually exclusive, a total of 18 (49%) patients showed mutations in the RTK pathway. These results suggest that activating mutations in the RTK pathway play a role in part as an additional event leading to the development of t(8;21) AML. The 6-year cumulative incidence of relapse in patients with RTK pathway mutations was 79.8%, compared with 13.5% in patients lacking such mutations (P=0.0029). Furthermore, the 6-year relapse-free survival in patients with mutations was 18% compared to 60% in those without mutations (P=0.0340), indicating that RTK mutations are associated with the clinical outcome in t(8;21) AML.

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Acknowledgements

We are very grateful to Drs Y Kanakura and M Mizuki for providing the cell line used in this study and Dr N Adachi for his kind help. We also thank Ms IM Nakayama for technical assistances. This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science and Culture, Grants-in-Aid for Cancer Research from the Japanese Ministry of Health and Welfare, and Public Trust Haraguchi Memorial Cancer Research Fund.

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Authors and Affiliations

  1. Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan

    T Nanri, N Matsuno, T Kawakita, H Mitsuya & N Asou

  2. Division of Hematology, NTT West Kyushu General Hospital, Kumamoto, Japan

    H Suzushima

  3. Institute for Clinical Research, Kumamoto Medical Center, National Hospital Organization, Kumamoto, Japan

    F Kawano

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Correspondence to N Asou.

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Nanri, T., Matsuno, N., Kawakita, T. et al. Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22). Leukemia 19, 1361–1366 (2005). https://doi.org/10.1038/sj.leu.2403803

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