International Journal of Hematology

, Volume 95, Issue 2, pp 167–175

Fyn is not essential for Bcr-Abl-induced leukemogenesis in mouse bone marrow transplantation models

Authors

  • Noriko Doki
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Jiro Kitaura
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Tomoyuki Uchida
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Daichi Inoue
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Yuki Kagiyama
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Katsuhiro Togami
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Masamichi Isobe
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Shinichi Ito
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Akie Maehara
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Kumi Izawa
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Naoko Kato
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Toshihiko Oki
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
    • Division of Stem Cell Signaling, The Institute of Medical ScienceThe University of Tokyo
  • Yuka Harada
    • Division of Hematology, Department of Internal MedicineKeio University School of Medicine
  • Fumio Nakahara
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
  • Hironori Harada
    • International Radiation Information Center, Research Institute for Radiation Biology and MedicineHiroshima University
    • Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of Tokyo
    • Division of Stem Cell Signaling, The Institute of Medical ScienceThe University of Tokyo
Original Article

DOI: 10.1007/s12185-011-0994-5

Cite this article as:
Doki, N., Kitaura, J., Uchida, T. et al. Int J Hematol (2012) 95: 167. doi:10.1007/s12185-011-0994-5

Abstract

The Bcr-Abl oncogene causes human Philadelphia chromosome-positive (Ph+) leukemias, including B-cell acute lymphoblastic leukemia (B-ALL) and chronic myeloid leukemia (CML) with chronic phase (CML-CP) to blast crisis (CML-BC). Previous studies have demonstrated that Src family kinases are required for the induction of B-ALL, but not for CML, which is induced by Bcr-Abl in mice. In contrast, it has been reported that Fyn is up-regulated in human CML-BC compared with CML-CP, implicating Fyn in the blast crisis transition. Here, we aimed to delineate the exact role of Fyn in the induction/progression of Ph+ leukemias. We found that Fyn is expressed in mouse hematopoietic cells at varying stages of development, including c-kit+Sca-1+Lin cells. Notably, Fyn is highly expressed in some of human lymphomas, but not in human Ph+ leukemias including CML-BC. In mouse bone marrow transplantation models, mice transplanted with wild-type or Fyn-deficient bone marrow cells transduced with Bcr-Abl showed no differences in the development of B-ALL or CML-like diseases. Similarly, Fyn deficiency failed to impact the development of myeloid CML-BC induced by Bcr-Abl and Hes1. Elevated expression of Fyn was not found in mouse samples of Bcr-Abl-mediated CML- and CML-BC-like diseases. Thus, Fyn is not required for the pathogenesis of Bcr-Abl-mediated leukemias.

Keywords

Ph+ leukemiasBcr-AblFyn

Copyright information

© The Japanese Society of Hematology 2011