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Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype

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Abstract

Mutations of nucleophosmin gene (NPM1) are known to be related to good prognosis in AML patients lacking FLT3 internal tandem duplication (FLT3-ITD). Recently, NPM1 mutations other than type A were reported, but their clinical significance is not well known. Retrospective medical record review of 106 de novo AML patients lacking FLT3-ITD, who received induction chemotherapy from three centers in Korea between 1997 and 2007, was performed. Direct sequencing of NPM1 and RT-PCR for FLT3-ITD was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for detection of mutations. NPM1 mutation was detected in 18 patients, where 13 were type A mutants and 5 were non-type A mutants. CR, CR1-D and OS was not different according to NPM1 mutational status overall. But, non-type A NPM1 mutation was related to shorter CR1-D when compared with NPM1 wild types and NPM1 type A mutation (p = 0.004). OS was shorter in non-type A mutants when compared with NPM1 wild-type patients and NPM1 type A mutants (p = 0.001). The type of mutation of NPM1 is important for prognosis in de novo AML lacking FLT3-ITD. Non-A type NPM1 mutation is a poor prognostic factor.

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Acknowledgment

This work was supported by a grant from Seoul National University Hospital Research Fund (No. 03-2006-003-0). This work was also supported by a grant from Cancer Research Institute, Seoul National University College of Medicine (No.800-20070121).

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea

    Youngil Koh, Inho Kim, Sung-Soo Yoon, Seonyang Park & Byoung Kook Kim

  2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

    Juwon Park, Kwang-Sung Ahn, Inho Kim, Sung-Soo Yoon, Seonyang Park & Byoung Kook Kim

  3. Department of Biomedical Science, Hanyang University College of Medicine, Seoul, Republic of Korea

    Eun-Kyung Bae

  4. Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

    Inho Kim, Sung-Soo Yoon, Seonyang Park & Byoung Kook Kim

  5. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Soo-Mee Bang

  6. Department of Internal Medicine, Gachon University College of Medicine Gil Hospital, Incheon, Republic of Korea

    Jae-Hoon Lee

  7. Department of Clinical Pathology, Seoul National University Hospital, Seoul, Republic of Korea

    Dong Soon Lee

  8. Department of Internal Medicine, Hanyang University Hospital, Seoul, Republic of Korea

    Young Yiul Lee

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  1. Youngil Koh
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  2. Juwon Park
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  3. Eun-Kyung Bae
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  8. Sung-Soo Yoon
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  10. Young Yiul Lee
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  11. Seonyang Park
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  12. Byoung Kook Kim
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Correspondence to Sung-Soo Yoon.

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Koh, Y., Park, J., Bae, EK. et al. Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype. Int J Hematol 90, 1–5 (2009). https://doi.org/10.1007/s12185-009-0350-1

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  • DOI: https://doi.org/10.1007/s12185-009-0350-1

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