Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation

Yasuo Mori, Goichi Yoshimoto, Takashi Kumano, Toshihiro Miyamoto, Tadafumi Iino, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Naoko Kinukawa, Koji Nagafuji, Takanori Teshima, Kazuya Shimoda, Koichi Akashi, Mine Harada

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Abstract

Objective: Patients with acute myelogenous leukaemia (AML) show co-existing frequently internal tandem duplications of FLT3 (FLT3-ITD) and mutations of nucleophosmin (NPM1-Mt). We investigated the biological and clinical significance of FLT3-ITD and/or NPM1-Mt in this context. Methods: We analysed 89 AML patients according to whether NPM1 and FLT3-ITD were single mutants, double mutants, or wild type for both. Results: FLT3-ITD was detected in 19 of 89 patients (21.3%), while NPM1-Mt was detected in 19 of 89 patients (21.3%); eight of 89 patients (9.0%) carried both FLT3-ITD and NPM1-Mt. By multivariate analysis, white blood cell count and peripheral blood blast cell count at diagnosis were significantly higher in patients with FLT3-ITD but not in those with only NPM1-Mt. NPM1-Mt was significantly related to female gender, normal karyotype, and M4 or M5 disease according to French-American-British criteria. In addition, leukaemic blast cells with NPM1-Mt, FLT3-ITD, or both expressed CD34 less frequently than wild-type blasts (P < 0.0001 and P = 0.005 respectively), while myelomonocytic markers such as CD11b and CD14 were expressed more frequently in patients with NPM1-Mt. Conclusion: FLT3-ITD may increase potential for cell proliferation to produce a leukaemic population; NPM1-Mt may cause cells to develop along the myelomonocytic lineage. Extensive analyses and detailed experiments will be required to clarify how NPM1 and FLT3 mutations interact in leukaemogenesis.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalEuropean Journal of Haematology
Volume79
Issue number1
DOIs
Publication statusPublished - Jul 1 2007

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Acute Myeloid Leukemia
Down-Regulation
Mutation
Blood Cell Count
nucleophosmin
Karyotype
Leukocyte Count
Multivariate Analysis
Cell Proliferation
Population

All Science Journal Classification (ASJC) codes

  • Hematology

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Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation. / Mori, Yasuo; Yoshimoto, Goichi; Kumano, Takashi; Miyamoto, Toshihiro; Iino, Tadafumi; Takenaka, Katsuto; Iwasaki, Hiromi; Harada, Naoki; Kinukawa, Naoko; Nagafuji, Koji; Teshima, Takanori; Shimoda, Kazuya; Akashi, Koichi; Harada, Mine.

In: European Journal of Haematology, Vol. 79, No. 1, 01.07.2007, p. 17-24.

Research output: Contribution to journalArticle

Mori, Yasuo ; Yoshimoto, Goichi ; Kumano, Takashi ; Miyamoto, Toshihiro ; Iino, Tadafumi ; Takenaka, Katsuto ; Iwasaki, Hiromi ; Harada, Naoki ; Kinukawa, Naoko ; Nagafuji, Koji ; Teshima, Takanori ; Shimoda, Kazuya ; Akashi, Koichi ; Harada, Mine. / Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation. In: European Journal of Haematology. 2007 ; Vol. 79, No. 1. pp. 17-24.
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abstract = "Objective: Patients with acute myelogenous leukaemia (AML) show co-existing frequently internal tandem duplications of FLT3 (FLT3-ITD) and mutations of nucleophosmin (NPM1-Mt). We investigated the biological and clinical significance of FLT3-ITD and/or NPM1-Mt in this context. Methods: We analysed 89 AML patients according to whether NPM1 and FLT3-ITD were single mutants, double mutants, or wild type for both. Results: FLT3-ITD was detected in 19 of 89 patients (21.3{\%}), while NPM1-Mt was detected in 19 of 89 patients (21.3{\%}); eight of 89 patients (9.0{\%}) carried both FLT3-ITD and NPM1-Mt. By multivariate analysis, white blood cell count and peripheral blood blast cell count at diagnosis were significantly higher in patients with FLT3-ITD but not in those with only NPM1-Mt. NPM1-Mt was significantly related to female gender, normal karyotype, and M4 or M5 disease according to French-American-British criteria. In addition, leukaemic blast cells with NPM1-Mt, FLT3-ITD, or both expressed CD34 less frequently than wild-type blasts (P < 0.0001 and P = 0.005 respectively), while myelomonocytic markers such as CD11b and CD14 were expressed more frequently in patients with NPM1-Mt. Conclusion: FLT3-ITD may increase potential for cell proliferation to produce a leukaemic population; NPM1-Mt may cause cells to develop along the myelomonocytic lineage. Extensive analyses and detailed experiments will be required to clarify how NPM1 and FLT3 mutations interact in leukaemogenesis.",
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T1 - Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation

AU - Mori, Yasuo

AU - Yoshimoto, Goichi

AU - Kumano, Takashi

AU - Miyamoto, Toshihiro

AU - Iino, Tadafumi

AU - Takenaka, Katsuto

AU - Iwasaki, Hiromi

AU - Harada, Naoki

AU - Kinukawa, Naoko

AU - Nagafuji, Koji

AU - Teshima, Takanori

AU - Shimoda, Kazuya

AU - Akashi, Koichi

AU - Harada, Mine

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Objective: Patients with acute myelogenous leukaemia (AML) show co-existing frequently internal tandem duplications of FLT3 (FLT3-ITD) and mutations of nucleophosmin (NPM1-Mt). We investigated the biological and clinical significance of FLT3-ITD and/or NPM1-Mt in this context. Methods: We analysed 89 AML patients according to whether NPM1 and FLT3-ITD were single mutants, double mutants, or wild type for both. Results: FLT3-ITD was detected in 19 of 89 patients (21.3%), while NPM1-Mt was detected in 19 of 89 patients (21.3%); eight of 89 patients (9.0%) carried both FLT3-ITD and NPM1-Mt. By multivariate analysis, white blood cell count and peripheral blood blast cell count at diagnosis were significantly higher in patients with FLT3-ITD but not in those with only NPM1-Mt. NPM1-Mt was significantly related to female gender, normal karyotype, and M4 or M5 disease according to French-American-British criteria. In addition, leukaemic blast cells with NPM1-Mt, FLT3-ITD, or both expressed CD34 less frequently than wild-type blasts (P < 0.0001 and P = 0.005 respectively), while myelomonocytic markers such as CD11b and CD14 were expressed more frequently in patients with NPM1-Mt. Conclusion: FLT3-ITD may increase potential for cell proliferation to produce a leukaemic population; NPM1-Mt may cause cells to develop along the myelomonocytic lineage. Extensive analyses and detailed experiments will be required to clarify how NPM1 and FLT3 mutations interact in leukaemogenesis.

AB - Objective: Patients with acute myelogenous leukaemia (AML) show co-existing frequently internal tandem duplications of FLT3 (FLT3-ITD) and mutations of nucleophosmin (NPM1-Mt). We investigated the biological and clinical significance of FLT3-ITD and/or NPM1-Mt in this context. Methods: We analysed 89 AML patients according to whether NPM1 and FLT3-ITD were single mutants, double mutants, or wild type for both. Results: FLT3-ITD was detected in 19 of 89 patients (21.3%), while NPM1-Mt was detected in 19 of 89 patients (21.3%); eight of 89 patients (9.0%) carried both FLT3-ITD and NPM1-Mt. By multivariate analysis, white blood cell count and peripheral blood blast cell count at diagnosis were significantly higher in patients with FLT3-ITD but not in those with only NPM1-Mt. NPM1-Mt was significantly related to female gender, normal karyotype, and M4 or M5 disease according to French-American-British criteria. In addition, leukaemic blast cells with NPM1-Mt, FLT3-ITD, or both expressed CD34 less frequently than wild-type blasts (P < 0.0001 and P = 0.005 respectively), while myelomonocytic markers such as CD11b and CD14 were expressed more frequently in patients with NPM1-Mt. Conclusion: FLT3-ITD may increase potential for cell proliferation to produce a leukaemic population; NPM1-Mt may cause cells to develop along the myelomonocytic lineage. Extensive analyses and detailed experiments will be required to clarify how NPM1 and FLT3 mutations interact in leukaemogenesis.

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