Details

Autor(en) / Beteiligte

• van der Weyden, Louise
• Giotopoulos, George
• Rust, Alistair G.
• Matheson, Louise S.
• van Delft, Frederik W.
• Kong, Jun
• Corcoran, Anne E.
• Greaves, Mel F.
• Mullighan, Charles G.
• Huntly, Brian J.
• Adams, David J.

Titel

Modeling the evolution of ETV6-RUNX1–induced B-cell precursor acute lymphoblastic leukemia in mice

Ist Teil von

• Blood, 2011-07, Vol.118 (4), p.1041-1051

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The t(12;21) translocation that generates the ETV6-RUNX1 (TEL-AML1) fusion gene, is the most common chromosomal rearrangement in childhood cancer and is exclusively associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The translocation arises in utero and is necessary but insufficient for the development of leukemia. Single-nucleotide polymorphism array analysis of ETV6-RUNX1 patient samples has identified multiple additional genetic alterations; however, the role of these lesions in leukemogenesis remains undetermined. Moreover, murine models of ETV6-RUNX1 ALL that faithfully recapitulate the human disease are lacking. To identify novel genes that cooperate with ETV6-RUNX1 in leukemogenesis, we generated a mouse model that uses the endogenous Etv6 locus to coexpress the Etv6-RUNX1 fusion and Sleeping Beauty transposase. An insertional mutagenesis screen was performed by intercrossing these mice with those carrying a Sleeping Beauty transposon array. In contrast to previous models, a substantial proportion (20%) of the offspring developed BCP-ALL. Isolation of the transposon insertion sites identified genes known to be associated with BCP-ALL, including Ebf1 and Epor, in addition to other novel candidates. This is the first mouse model of ETV6-RUNX1 to develop BCP-ALL and provides important insight into the cooperating genetic alterations in ETV6-RUNX1 leukemia.