Fyn is not essential for Bcr-Abl-induced leukemogenesis in mouse bone marrow transplantation models
First Online: 22 December 2011 Received: 09 October 2011 Revised: 06 December 2011 Accepted: 07 December 2011 DOI:
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 + leukemias Bcr-Abl Fyn References
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