Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

"PIM1" gene cooperates with human "BCL6" gene to promote the development of lymphomas

Beverly W. Baron, John Anastasi, Elizabeth M. Hyjek, Juraj Bies, Poluru L. Reddy, Jingfang Dong, Loren Joseph, Michael J. Thirman, Kristen Wroblewski, Linda Wolff and Joseph M. Baron
Proceedings of the National Academy of Sciences of the United States of America
Vol. 109, No. 15 (April 10, 2012), pp. 5735-5739
Stable URL: http://www.jstor.org/stable/41588234
Page Count: 5
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
"PIM1" gene cooperates with human "BCL6" gene to promote the development of lymphomas
Preview not available

Abstract

Diffuse large B-cell lymphomas in humans are associated with chromosomal rearrangements (~40%) and/or mutations disrupting autoregulation (~16%) involving the BCL6 gene. Studies of lymphoma development in humans and mouse models have indicated that lymphomagenesis evolves through the accumulation of multiple genetic alterations. Based on our prior studies, which indicated that carcinogen-induced DNA mutations enhance the incidence of lymphomas in our mouse model expressing a human BCL6 transgene, we hypothesized that mutated genes are likely to play an important cooperative role in BCL6-associated lymphoma development. We used retroviral insertional mutagenesis in an effort to identify which genes cooperate with BCL6 in lymphomagenesis in our BCL6 transgenic mice. We identified PIM1 as the most frequently recurring cooperating gene in our murine BCL6-associated lymphomas (T-and B-cell types), and we observed elevated levels of PIM1 mRNA and protein expression in these neoplasms. Further, immunohistochemical staining, which was performed in 20 randomly selected BCL6-positive human B-and T-cell lymphomas, revealed concurrent expression of BCL6 and PIM1 in these neoplasms. As PIM1 encodes a serine/threonine kinase, PIM1 kinase inhibition may be a promising therapy for BCL6/PIM1-positive human lymphomas.

Page Thumbnails

  • Thumbnail: Page 
[5735]
    [5735]
  • Thumbnail: Page 
5736
    5736
  • Thumbnail: Page 
5737
    5737
  • Thumbnail: Page 
5738
    5738
  • Thumbnail: Page 
5739
    5739