Activation of c-myb by 5' retrovirus promoter insertion in myeloid neoplasms is dependent upon an intact alternative splice donor site (SD') in gag

Journal Article · Mon Dec 20 04:00:00 EST 2004 · Virology

DOI:https://doi.org/10.1016/j.virol.2004.09.038· OSTI ID:20637185

Ramirez, Jean Marie ^[1]; Houzet, Laurent ^[1]; Koller, Richard ^[2]; Bies, Juraj ^[2]; Wolff, Linda ^[2]; Mougel, Marylene ^[1]

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1. Laboratoire Infections Retrovirales et Signalisation Cellulaire, CNRS UMR5121, UMI, IFR122, Montpellier (France)
2. Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD 20892-4263 (United States)

Alternative splicing in Mo-MuLV recruits a splice donor site, SD', within the gag that is required for optimal replication in vitro. Remarkably, this SD' site was also found to be utilized for production of oncogenic gag-myb fusion RNA in 100% of murine-induced myeloid leukemia (MML) in pristane-treated BALB/c mice. Therefore, we investigated the influence of silent mutations of SD' in this model. Although there was no decrease in the overall incidence of disease, there was a decrease in the incidence of myeloid leukemia with a concomitant increase in lymphoid leukemia. Importantly, there was a complete lack of myeloid tumors associated with 5' insertional mutagenic activation of c-myb, suggesting the specific requirement of the SD' site in this mechanism.

• OSTI ID: 20637185
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 330; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
IN VITRO
LYMPHOMAS
MICE
MUTATIONS
MYELOID LEUKEMIA
ONCOGENES
PROMOTERS
RNA