Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice

DA Dedera, EK Waller, DP LeBrun, A Sen-Majumdar… - Cell, 1993 - cell.com
DA Dedera, EK Waller, DP LeBrun, A Sen-Majumdar, ME Stevens, GS Barsh, ML Cleary
Cell, 1993cell.com
Expression of the homeobox fusion gene E2A-PBXl under control of the immunoglobulin
heavy chain enhancer efficiently induced malignancies in transgenic mice. All animals died
before 5 months of age with lymphomas that demonstrated phenotypes consistent with
transitional intermediate thymocytes (CD4+/CD8+/CD3med). E2A-PBXI also markedly
altered lymphoid development in pretumorous animals, reducing the number of thymocytes
and bone marrow B lineage progenitors to 20% of normal levels. In spite of the observed …
Summary
Expression of the homeobox fusion gene E2A-PBXl under control of the immunoglobulin heavy chain enhancer efficiently induced malignancies in transgenic mice. All animals died before 5 months of age with lymphomas that demonstrated phenotypes consistent with transitional intermediate thymocytes (CD4+/CD8+/CD3med). E2A-PBXI also markedly altered lymphoid development in pretumorous animals, reducing the number of thymocytes and bone marrow B lineage progenitors to 20% of normal levels. In spite of the observed reductions in lymphoid cells, premalignant animals contained significantly increased numbers of cycling thymocytes, but a higher proportion was also undergoing apoptosis, suggesting that increased cell death resulted in the marked lymphopenias. These data indicate that the chlmeric homeodomain protein EZA-PBXl paradoxically induces both proliferation and apoptosis in lymphoid cells, suggesting an in vivo association between nuclear oncogene-induced cell cycle progression and programed cell death.
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