Loss of Gadd45b accelerates BCR-ABL-driven CML
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Xiaojin Sha1,*, Barbara Hoffman1,* and Dan A. Liebermann1,2
1Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA, USA
2Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
*These authors have contributed equally to this work
Dan A. Liebermann, email: email@example.com
Keywords: Gadd45a; chronic myelogenous leukemia; stress response protein; tumor suppressor
Received: July 23, 2018 Accepted: July 28, 2018 Published: September 07, 2018
Gadd45b is a member of Gadd45 stress sensor protein family that also includes Gadd45a and Gadd45g. To investigate the effect of Gadd45b in bcr-abl oncogene driven chronic myeloid leukemia (CML) development, syngeneic wild type lethally irradiated mice were reconstituted with either wild type or Gadd45b null myeloid progenitors transduced with a retroviral vector expressing BCR-ABL. Loss of Gadd45b was observed to accelerate BCR-ABL driven CML development with shortened median mouse survival time. BCR-ABL Gadd45b deficient CML progenitors exhibited increased proliferation and decreased apoptosis, associated with hyper-activation of c-Jun NH2-terminal kinase and Stat5. These results provide novel evidence that gadd45b, like gadd45a, functions as a suppressor of BCR-ABL driven leukemia, albeit via a different mechanism.
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