Modeling BCR/ABL-Driven Malignancies in the Mouse
In this chapter, we describe model systems to study leukemia driven by the Abelson oncogene. In people, the Abelson oncogene results from the chromosomal translocation t(9;22)(q34;q11) that is found in more than 90 % of all human chronic myeloid leukemia (CML) patients and in 20–25 % of patients suffering from acute lymphoid leukemia (ALL). This translocation is also called Philadelphia chromosome and encodes the BCR/ABL oncogene, a constitutive active tyrosine kinase. BCR/ABL renders hematopoietic cells independent from exogenous growth-stimulatory signals by continuously engaging signaling pathways including JAK-STAT signaling and the MAPK pathway. The enforced expression of BCR/ABL suffices to transform hematopoietic cells which made it to one of the best studied model systems in the field. Here we present methods to study BCR/ABL-triggered leukemia and solid lymphoid tumor formation.
Key wordsBCR/ABL v-ABL Leukemia CML ALL Solid lymphoid tumors BM transplantation
The authors are grateful to all current and former lab members of the Institute of Pharmacology and Toxicology at the University of Veterinary Medicine, Vienna. We are indebted to Sabine Fajmann for excellent technical assistance and all animal caretakers for taking excellent care of the mice. We further thank Mathias Müller, Birgit Strobl, Thomas Decker, Richard Moriggl, Robert Eferl, Emilio Casanova, and Dagmar Stoiber for valuable scientific input. This work was supported by the Austrian Science Foundation (FWF) by two grants to V.S. (SFB F28 and SFB F47).
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