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Acute Leukemias

Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia

Leukemia volume 25, pages 1423–1432 (2011)Cite this article

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Abstract

Recently, c-kit mutations have been reported as a novel adverse prognostic factor of acute myeloid leukemia with t(8;21)(q22;q22) translocation (t(8;21) AML). However, much remains unclear about its clinical significance. In this study, we developed a highly sensitive mutation detection method known as mutation-biased PCR (MB-PCR) and investigated the relationship between c-kit mutations and prognosis. When c-kit mutations were analyzed for 26 cases of t(8;21) AML using the direct sequence (DS) and MB-PCR, the latter had a much higher detection rate of c-kit mutations at initial presentation (DS 5/26(19.2%) vs MB-PCR 12/26(46.2%)). Interestingly for the three cases, in which c-kit mutations were observed only at relapse with the DS, c-kit mutations were detected at initial presentation using the MB-PCR. This result suggests that a minor leukemia clone with c-kit mutations have resistance to treatment and are involved in relapse. In univariate analyses, the presence of a c-kit mutation using DS was not an adverse prognostic factor (P=0.355), but was a factor when using MB-PCR (P=0.014). The presence of c-kit mutations with MB-PCR was also an independent adverse prognostic factor by multivariate analyses (P=0.006). We conclude that sensitivity of c-kit mutation detection method is important to predict prognosis for t(8;21) AML.

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Acknowledgements

We thank Mitsuharu Hirai, Mariko Komori and ARKRAY, Inc. (Kyoto, Japan) for technical contribution to this work and providing QProbe and prototype of i-densy. SW and HY were the principal investigator and takes primary responsibility for the paper. SW, HY, KD and KI recruited the patients. SW, HY, YM and FK performed the laboratory work for this study. SW, HY, KD, KM and KI analyzed the data and wrote the paper. SW and HY contributed equally this work.

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  1. S Wakita and H Yamaguchi: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

    S Wakita, H Yamaguchi, Y Mitamura, F Kosaka, K Dan & K Inokuchi

  2. Division of Gene Therapy Research Center for Advanced Medical Technology, Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan

    K Miyake

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Wakita, S., Yamaguchi, H., Miyake, K. et al. Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia. Leukemia 25, 1423–1432 (2011). https://doi.org/10.1038/leu.2011.104

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