Original Article

International Journal of Hematology

, Volume 95, Issue 2, pp 167-175

First online:

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

  • Noriko DokiAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Jiro KitauraAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Tomoyuki UchidaAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Daichi InoueAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Yuki KagiyamaAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Katsuhiro TogamiAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Masamichi IsobeAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Shinichi ItoAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
  • , Akie MaeharaAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
    • , Kumi IzawaAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
    • , Naoko KatoAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
    • , Toshihiko OkiAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of TokyoDivision of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo
    • , Yuka HaradaAffiliated withDivision of Hematology, Department of Internal Medicine, Keio University School of Medicine
    • , Fumio NakaharaAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo
    • , Hironori HaradaAffiliated withInternational Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University
    • , Toshio KitamuraAffiliated withDivision of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of TokyoDivision of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo Email author 

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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