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- Title
Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation.
- Authors
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
- Abstract
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.
- Subjects
LEUKEMIA; CELL proliferation; BLOOD cells; LEUCOCYTES; KILLER cells; BLOOD testing
- Publication
European Journal of Haematology, 2007, Vol 79, Issue 1, p17
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/j.1600-0609.2007.00866.x