Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia

Tatsuya Suzuki, Hitoshi Kiyoi, Kazutaka Ozeki, Akihiro Tomita, Satomi Yamaji, Ritsuro Suzuki, Yoshihisa Kodera, Shuichi Miyawaki, Norio Asou, Kazutaka Kuriyama, Fumiharu Yagasaki, Chihiro Shimazaki, Hideki Akiyama, Miki Nishimura, Toshiko Motoji, Katsuji Shinagawa, Akihiro Takeshita, Ryuzo Ueda, Tomohiro Kinoshita, Nobuhiko EmiTomoki Naoe

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.

Original languageEnglish
Pages (from-to)2854-2861
Number of pages8
JournalBlood
Volume106
Issue number8
DOIs
Publication statusPublished - 01-10-2005

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Acute Myeloid Leukemia
Genes
Mutation
Chemotherapy
Recurrence
Leukemia
Gene Duplication
Karyotype
Cytogenetics
nucleophosmin
Japan
Multivariate Analysis
Clone Cells
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Suzuki, Tatsuya ; Kiyoi, Hitoshi ; Ozeki, Kazutaka ; Tomita, Akihiro ; Yamaji, Satomi ; Suzuki, Ritsuro ; Kodera, Yoshihisa ; Miyawaki, Shuichi ; Asou, Norio ; Kuriyama, Kazutaka ; Yagasaki, Fumiharu ; Shimazaki, Chihiro ; Akiyama, Hideki ; Nishimura, Miki ; Motoji, Toshiko ; Shinagawa, Katsuji ; Takeshita, Akihiro ; Ueda, Ryuzo ; Kinoshita, Tomohiro ; Emi, Nobuhiko ; Naoe, Tomoki. / Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. In: Blood. 2005 ; Vol. 106, No. 8. pp. 2854-2861.
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abstract = "Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9{\%}) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.",
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Suzuki, T, Kiyoi, H, Ozeki, K, Tomita, A, Yamaji, S, Suzuki, R, Kodera, Y, Miyawaki, S, Asou, N, Kuriyama, K, Yagasaki, F, Shimazaki, C, Akiyama, H, Nishimura, M, Motoji, T, Shinagawa, K, Takeshita, A, Ueda, R, Kinoshita, T, Emi, N & Naoe, T 2005, 'Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia', Blood, vol. 106, no. 8, pp. 2854-2861. https://doi.org/10.1182/blood-2005-04-1733

Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. / Suzuki, Tatsuya; Kiyoi, Hitoshi; Ozeki, Kazutaka; Tomita, Akihiro; Yamaji, Satomi; Suzuki, Ritsuro; Kodera, Yoshihisa; Miyawaki, Shuichi; Asou, Norio; Kuriyama, Kazutaka; Yagasaki, Fumiharu; Shimazaki, Chihiro; Akiyama, Hideki; Nishimura, Miki; Motoji, Toshiko; Shinagawa, Katsuji; Takeshita, Akihiro; Ueda, Ryuzo; Kinoshita, Tomohiro; Emi, Nobuhiko; Naoe, Tomoki.

In: Blood, Vol. 106, No. 8, 01.10.2005, p. 2854-2861.

Research output: Contribution to journalArticle

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T1 - Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia

AU - Suzuki, Tatsuya

AU - Kiyoi, Hitoshi

AU - Ozeki, Kazutaka

AU - Tomita, Akihiro

AU - Yamaji, Satomi

AU - Suzuki, Ritsuro

AU - Kodera, Yoshihisa

AU - Miyawaki, Shuichi

AU - Asou, Norio

AU - Kuriyama, Kazutaka

AU - Yagasaki, Fumiharu

AU - Shimazaki, Chihiro

AU - Akiyama, Hideki

AU - Nishimura, Miki

AU - Motoji, Toshiko

AU - Shinagawa, Katsuji

AU - Takeshita, Akihiro

AU - Ueda, Ryuzo

AU - Kinoshita, Tomohiro

AU - Emi, Nobuhiko

AU - Naoe, Tomoki

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.

AB - Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.

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