Skip NavigationSkip to Content
Return Return to Search Results

Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy

  1. Author:
    Dave, U. P.
    Akagi, K.
    Tripathi, R.
    Clevel, S. M.
    Thompson, M. A.
    Yi, M.
    Stephens, R.
    Downing, J. R.
    Jenkins, N. A.
    Copeland, N. G.

  2. Author Address

    Dave, Utpal P.; Tripathi, Rati, Cleveland, Susan M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37203 USA. [Dave, Utpal P.; Tripathi, Rati, Cleveland, Susan M.] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN USA. [Akagi, Keiko] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Thompson, Mary A.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Yi, Ming, Stephens, Robert] Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD USA. [Downing, James R.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 0511, Singapore.
    1. Year: 2009
  2. Journal: Plos Genetics
    1. 5
    2. 5
    3. Pages: 1-13
  4. Type of Article: Article
  1. Abstract:

    Five X-linked severe combined immunodeficiency patients (SCID-X1) successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2. Genetic evidence also suggests a role for IL2RG in tumor formation, although this remains controversial. Here, we show that the genes and signaling pathways deregulated in murine leukemias with retroviral insertions at Lmo2 are similar to those deregulated in human leukemias with high LMO2 expression and are highly predictive of the leukemias induced in SCID-X1 patients. We also provide additional evidence supporting the notion that IL2RG and LMO2 cooperate in leukemia induction but are not sufficient and require additional cooperating mutations. The highly concordant nature of the genetic events giving rise to mouse and human leukemias with mutations at Lmo2 are an encouraging sign to those wanting to use mice to model human cancer and may help in designing safer methods for retroviral gene therapy.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1371/journal.pgen.1000491
  3. PMID: 19461887

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel