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Synergy of Myc, cell cycle regulators and the Akt pathway in the development of aggressive B-cell lymphoma in a mouse model

Leukemia volume 28, pages 2270–2272 (2014)Cite this article

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The accumulation of multiple genetic abnormalities can result in hematological malignancies. With regard to B-cell lymphomas, chromosomal translocations, copy number alterations and abnormal gene expression were shown to be involved in lymphomagenesis.1 Furthermore, numerous gene mutations are being found by high-throughput sequencing.2, 3, 4 Broad and intensive functional analyses are required to delineate the degree to which specific genetic alterations contribute to the development of lymphomas, although it is not an easy task to elucidate the synergistic effects of candidate genes employing currently available methods such as those employing transgenic or knockout mice. Moreover, additional genetic changes sometimes occur in lymphomas developing in genetically modified mice,5 which make it difficult to determine the minimum genetic abnormalities required for tumor development.

In an effort to identify the genes required for the transformation of normal B cells into malignant cells, we have established in vitro culture systems that allow gene transduction into normal murine pre-B cells6 and mature B cells.7 These systems successfully showed the synergistic effects of deregulated translocation-associated genes on the development of lymphoma in vivo. In the present study, we have focused on gene mutations, and have aimed to provide direct evidence of the synergy of Myc, cell cycle regulators and the Akt pathway in the development of lymphoma in a mouse model.

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Acknowledgements

We thank Ms Seiko Sato for her tremendous help with the animal husbandry; Kyoko Hirano and Yumiko Kasugai for technical assistance; and Drs Kennosuke Karube, Miyuki Suguro-Katayama, Noriaki Yoshida, Tatsuo Kakiuchi and Taishi Takahara for critical discussions and encouragement throughout the study. myrAkt cDNA was kindly provided by Dr U Kikkawa (Kobe University). This work was supported by a Health Labour Sciences Research Grant from The Ministry of Health, Labour and Welfare (ST, KO and MS), a Grant-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology (MS) and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (ST and MS).

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Author notes

  1. K Arita and S Tsuzuki: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan

    K Arita, S Tsuzuki & M Seto

  2. Third Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    K Arita & T Sugiyama

  3. Department of Pathology, School of Medicine, Kurume University, Kurume, Japan

    K Ohshima & M Seto

  4. Department of Cancer Genetics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    M Seto

Authors
  1. K Arita
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  2. S Tsuzuki
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  3. K Ohshima
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  4. T Sugiyama
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  5. M Seto
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Corresponding author

Correspondence to S Tsuzuki.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Arita, K., Tsuzuki, S., Ohshima, K. et al. Synergy of Myc, cell cycle regulators and the Akt pathway in the development of aggressive B-cell lymphoma in a mouse model. Leukemia 28, 2270–2272 (2014). https://doi.org/10.1038/leu.2014.224

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