Skip to main content

Open Access Effect of FLT3 Ligand on Survival and Disease Phenotype in Murine Models Harboring a FLT3 Internal Tandem Duplication Mutation

Download Article:
 Download
(PDF 389.4345703125 kb)
 
Many of the mutations contributing to leukemogenesis in acute myeloid leukemia have been identified. A common activating mutation is an internal tandem duplication (ITD) mutation in the FLT3 gene that is found in approximately 25% of patients and confers a poor prognosis. FLT3 inhibitors have been developed and have some efficacy, but patients often relapse. Levels of FLT3 ligand (FL) are significantly elevated in patients during chemotherapy and may be an important component contributing to relapse. We used a mouse model to investigate the possible effect of FL expression on leukemogenesis involving FLT3-ITD mutations in an in vivo system. FLT3ITD/ITD FL–/– (knockout) mice had a statistically significant increase in survival compared with FLT3ITD/ITD FL+/+ (wildtype) mice, most of which developed a fatal myeloproliferative neoplasm. These findings suggest that FL levels may have prognostic significance in human patients. We also studied the effect of FL expression on survival in a FLT3-ITD NUP98–HOX13 (NHD13) fusion mouse model. These mice develop an aggressive leukemia with short latency. We asked whether FL expression played a similar role in this context. The NUP98-HOX13 FLT3ITD/wt FL–/– mice did not have a survival advantage, compared with NUP98-HOX13 FLT3ITD/wt FL+/+ mice (normal FL levels). The loss of the survival advantage of the FL knockout group in the NUP98–HOX13 model suggests that adding a second mutation changes the effect of FL expression in the context of more aggressive disease.
No References for this article.
No Supplementary Data.
No Data/Media
No Metrics

Document Type: Research Article

Affiliations: 1: Department of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3: Department of Genetics Branch, National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA 4: Department of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. donsmall@jhmi.edu

Publication date: 2013-06-01

More about this publication?
  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

    Attention Members: To access the full text of the articles, be sure you are logged in to the AALAS website.

    Attention: please note, due to a temporary technical problem, reference linking within the content is not available at this time

  • Editorial Board
  • Information for Authors
  • Submit a Paper
  • Subscribe to this Title
  • Membership Information
  • Information for Advertisers
  • For issues prior to 1998
  • Institutional Subscription Activation
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more