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Novel mutations in the FLT3 gene in adult patients with refractory acute myeloid leukemia

Leukemia volume 19, pages 141–143 (2005)Cite this article

TO THE EDITOR

We studied 11 adult patients with AML who were primarily refractory to standard chemotherapy: four patients (36%) showed FLT3-ITD mutations and the four ITD mutants sequenced showed different duplications. The mutant sequences found in these four patients were all novel (Table 3). Two of these four patients had duplication mutations, and the other two patients showed ITD mutations with both duplication and tandem insertion. Sequence analysis of ITD mutation bands revealed in-frame duplications between 40 and 105 bases in the JM domain. In one of the four patients, the ITD mutation did not cause a transcription error, but in the other three patients the mutations corresponded to amino-acid changes. Mutations in the JM domain, or activating loop mutations, result in the constitutive activation of FLT3 kinase, which is strongly associated with leukocytosis and poor prognosis in AML patients. Four patients with ITD showed poor treatment response as has been reported.2 The ITD mutations of AML patients have shown variable rates in other studies. Also our four ITD mutation patients contained the JM domain. However, interestingly, we could not find a D835 mutation in this study, but there were many kinds of duplications at different locations with different sizes.

Table 3 Sequence analysis of FLT3-ITD in AML
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Acknowledgements

We acknowledge financial support from the Catholic Medical Center Research Foundation made in the program year 2002.

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  1. Division of Hematology, Department of Internal-Medicine, Catholic Hemopoietic Stem Cell Transplantation Center, St Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea

    Y Choi, H-J Kim, B-H Park, W-S Min & C-C Kim

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Correspondence to H-J Kim.

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Choi, Y., Kim, HJ., Park, BH. et al. Novel mutations in the FLT3 gene in adult patients with refractory acute myeloid leukemia. Leukemia 19, 141–143 (2005). https://doi.org/10.1038/sj.leu.2403580

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