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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.
    Author: Mori Y, Yoshimoto G, Kumano T, Miyamoto T, Iino T, Takenaka K, Iwasaki H, Harada N, Kinukawa N, Nagafuji K, Teshima T, Shimoda K, Akashi K, Harada M.
    Journal: Eur J Haematol; 2007 Jul; 79(1):17-24. PubMed ID: 17598835.
    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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