International Journal of Hematology

, Volume 95, Issue 2, pp 167–175 | Cite as

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

  • Noriko Doki
  • Jiro Kitaura
  • Tomoyuki Uchida
  • Daichi Inoue
  • Yuki Kagiyama
  • Katsuhiro Togami
  • Masamichi Isobe
  • Shinichi Ito
  • Akie Maehara
  • Kumi Izawa
  • Naoko Kato
  • Toshihiko Oki
  • Yuka Harada
  • Fumio Nakahara
  • Hironori Harada
  • Toshio Kitamura
Original Article
First Online:
Received:
Revised:
Accepted:

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+ leukemias Bcr-Abl Fyn 
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Notes

Acknowledgments

We are grateful to Dr Dovie Wylie for her excellent editing of our English. We thank Dr Tadashi Yamamoto for providing Fyn −/− mice. This work was supported by the Ministry of Education, Science, Technology, Sports and Culture, Japan.

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Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Noriko Doki
    • 1
  • Jiro Kitaura
    • 1
  • Tomoyuki Uchida
    • 1
  • Daichi Inoue
    • 1
  • Yuki Kagiyama
    • 1
  • Katsuhiro Togami
    • 1
  • Masamichi Isobe
    • 1
  • Shinichi Ito
    • 1
  • Akie Maehara
    • 1
  • Kumi Izawa
    • 1
  • Naoko Kato
    • 1
  • Toshihiko Oki
    • 1
    • 2
  • Yuka Harada
    • 3
  • Fumio Nakahara
    • 1
  • Hironori Harada
    • 4
  • Toshio Kitamura
    • 1
    • 2
  1. 1.Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  2. 2.Division of Stem Cell Signaling, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.Division of Hematology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
  4. 4.International Radiation Information Center, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan

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