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AML with t(8;21) and trisomy 4: possible involvement of c-kit?

Leukemia volume 17, page 1915 (2003)Cite this article

TO THE EDITOR

Nishii et al1 have recently described a minor subset of acute myeloid leukemia (AML) patients with t(8;21) and trisomy 4, who had a relatively poor prognosis when compared to t(8;21) AML patients with or without other cytogenetic abnormalities. A review of the literature suggests a possible mechanism for this poor prognosis. Current theory regarding the pathogenesis of AML, especially in those patients with either a t(8;21)(q22;q22) or inv(16)(p13q22) abnormality, has postulated the cooperativity of core-binding factor (CBF) gene rearrangements (AML1-ETO and CBFB-MYH11, respectively) with mutations in those genes encoding receptor tyrosine kinases (eg FLT3, KIT).2 In particular, mutations of the c-kit gene, located at chromosome 4q11–q12, have been detected in a significant proportion of patients with CBF-AML3 and also in two patients with t(8;21) and trisomy 4.4 In one of these latter patients, the trisomy 4 lead to duplication and thus increased dosage of the mutated c-kit allele,5 suggesting an additional mechanism of leukemogenesis. This observation is supported by evidence of amplification of a c-kit mutation in the t(8;21) and trisomy four-positive cell line Kasumi-1.6 Further investigation is therefore warranted to determine the presence of c-kit mutations in the three t(8;21) AML patients with trisomy 4 described by Nishii et al,1 as the most common activating mutation of c-kit has been show to confer drug resistance,7 which could be partly responsible for the relatively poor prognosis. If mutations are present, these patients may be eligible for additional treatment with novel therapies that inhibit KIT tyrosine kinase activity.8

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References

  1. Nishii K, Usui E, Katayama N, Lorenzo F, Nakase K, Kobayashi T et al. Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML. Leukemia 2003; 17: 731–737.

    Article  CAS  Google Scholar 

  2. Speck NA, Gilliland DG . Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer 2002; 2: 502–513.

    Article  CAS  Google Scholar 

  3. Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D et al. C-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol 1999; 105: 894–900.

    Article  CAS  Google Scholar 

  4. Beghini A, Peterlongo P, Ripamonti CB, Larizza L, Cairoli R, Morra E et al. C-kit mutations in core binding factor leukemias. Blood 2000; 95: 726–727.

    CAS  PubMed  Google Scholar 

  5. Beghini A, Ripamonti CB, Castorina P, Pezzetti L, Doneda L, Cairoli R et al. Trisomy 4 leading to a duplication of a mutated KIT allele in acute myeloid leukemia with mast cell involvement. Cancer Genet Cytogenet 2000; 119: 26–31.

    Article  CAS  Google Scholar 

  6. Beghini A, Magnani I, Ripamonti CB, Larizza L . Amplification of a novel c-kit activating mutation Asn822-Lys in the Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia. Hematology J 2002; 3: 157–163.

    Article  CAS  Google Scholar 

  7. Ning ZQ, Li J, Arceci RJ . Activating mutations of c-kit at codon 816 confer drug resistance in human leukemia cells. Leukemia Lymphoma 2001; 41: 513–522.

    Article  CAS  Google Scholar 

  8. Heinrich MC, Blanke CD, Druker BJ, Corless CL . Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 2002; 20: 1692–1703.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Leukaemia Research Fund Centre, Institute of Cancer Research, London, UK

    S E Langabeer

  2. Department of Biology and Genetics, Medical Faculty, University of Milan, Milan, Italy

    A Beghini & L Larizza

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  1. S E Langabeer
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  2. A Beghini
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  3. L Larizza
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Langabeer, S., Beghini, A. & Larizza, L. AML with t(8;21) and trisomy 4: possible involvement of c-kit?. Leukemia 17, 1915 (2003). https://doi.org/10.1038/sj.leu.2403066

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