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Mouse Models of Cancer pp 263–282Cite as

Modeling BCR/ABL-Driven Malignancies in the Mouse

Part of the Methods in Molecular Biology book series (MIMB,volume 1267)

Abstract

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 words

  • BCR/ABL
  • v-ABL
  • Leukemia
  • CML
  • ALL
  • Solid lymphoid tumors
  • BM transplantation

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  • DOI: 10.1007/978-1-4939-2297-0_12
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References

  1. Chan LC, Karhi KK, Rayter SI et al (1987) A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. Nature 325:635–637

    CAS  PubMed  CrossRef  Google Scholar 

  2. Lichty BD, Keating A, Callum J et al (1998) Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. Br J Haematol 103:711–715

    CAS  PubMed  CrossRef  Google Scholar 

  3. Clark SS, McLaughlin J, Crist WM et al (1987) Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL. Science 235:85–88

    CAS  PubMed  CrossRef  Google Scholar 

  4. Chung SW, Wong PM, Durkin H et al (1991) Leukemia initiated by hemopoietic stem cells expressing the v-abl oncogene. Proc Natl Acad Sci U S A 88:1585–1589

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  5. Vesely MD, Kershaw MH, Schreiber RD et al (2011) Natural innate and adaptive immunity to cancer. Annu Rev Immunol 29:235–271

    CAS  PubMed  CrossRef  Google Scholar 

  6. Chen M, Gallipoli P, DeGeer D et al (2013) Targeting primitive chronic myeloid leukemia cells by effective inhibition of a new AHI-1-BCR-ABL-JAK2 complex. J Natl Canc Inst 105:405–423

    CAS  CrossRef  Google Scholar 

  7. Warsch W, Grundschober E, Berger A et al (2012) STAT5 triggers BCR-ABL1 mutation by mediating ROS production in chronic myeloid leukaemia. Oncotarget 3:1669–1687

    PubMed Central  PubMed  Google Scholar 

  8. Berger A, Hoelbl-Kovacic A, Bourgeais J et al (2013) PAK-dependent STAT5 serine phosphorylation is required for BCR-ABL-induced leukemogenesis. Leukemia 28:629–641

    Google Scholar 

  9. Putz EM, Gotthardt D, Hoermann G et al (2013) CDK8-mediated STAT1-S727 phosphorylation restrains NK cell cytotoxicity and tumor surveillance. Cell Rep 4:437–444

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  10. Kollmann K, Heller G, Schneckenleithner C et al (2013) A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer Cell 24:167–181

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  11. Hoelbl A, Kovacic B, Kerenyi MA et al (2006) Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood 107:4898–4906

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  12. Warsch W, Kollmann K, Eckelhart E et al (2011) High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia. Blood 117:3409–3420

    CAS  PubMed  CrossRef  Google Scholar 

  13. Friedbichler K, Kerenyi MA, Kovacic B et al (2010) Stat5a serine 725 and 779 phosphorylation is a prerequisite for hematopoietic transformation. Blood 116:1548–1558

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  14. Kollmann K, Heller G, Ott RG et al (2011) c-JUN promotes BCR-ABL-induced lymphoid leukemia by inhibiting methylation of the 5′ region of Cdk6. Blood 117:4065–4075

    CAS  PubMed  CrossRef  Google Scholar 

  15. Hantschel O, Warsch W, Eckelhart E et al (2012) BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. Nat Chem Biol 8:285–293

    CAS  PubMed  CrossRef  Google Scholar 

  16. Hoelbl A, Schuster C, Kovacic B et al (2010) Stat5 is indispensable for the maintenance of bcr/abl -positive leukaemia. EMBO Mol Med 2:98–110

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  17. Kovacic B, Stoiber D, Moriggl R et al (2006) STAT1 acts as a tumor promoter for leukemia development. Cancer Cell 10:77–87

    CAS  PubMed  CrossRef  Google Scholar 

  18. Ott RG, Simma O, Kollmann K et al (2007) JunB is a gatekeeper for B-lymphoid leukemia. Oncogene 26:4863–4871

    CAS  PubMed  CrossRef  Google Scholar 

  19. Rosenberg N, Baltimore D (1976) A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus. J Exp Med 143:1453–1463

    CAS  PubMed  CrossRef  Google Scholar 

  20. Serunian LA, Rosenberg N (1986) Abelson virus potentiates long-term growth of mature B lymphocytes. Mol Cell Biol 6:183–194

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Kovacic B, Hoelbl A, Litos G et al (2012) Diverging fates of cells of origin in acute and chronic leukaemia. EMBO Mol Med 4:283–297

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  22. Baron F, Turhan AG, Giron-Michel J et al (2002) Leukemic target susceptibility to natural killer cytotoxicity: relationship with BCR-ABL expression. Blood 99:2107–2113

    CAS  PubMed  CrossRef  Google Scholar 

  23. Stoiber D, Kovacic B, Schuster C et al (2004) TYK2 is a key regulator of the surveillance of B lymphoid tumors. J Clin Invest 114:1650–1658

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

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Acknowledgments

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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Authors and Affiliations

  1. University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria

    Christine Schneckenleithner, Andrea Hoelbl-Kovacic & Veronika Sexl

Authors
  1. Christine Schneckenleithner
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  2. Andrea Hoelbl-Kovacic
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  3. Veronika Sexl
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Corresponding author

Correspondence to Veronika Sexl .

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Editors and Affiliations

  1. Medical University Vienna (MUV) Institute for Cancer Research, Vienna, Austria

    Robert Eferl

  2. Research (LBI-CR), Medical University Vienna (MUV), Center of Physiology and Pharmacology & Ludwig Boltzmann Institute for Cancer, Vienna, Austria

    Emilio Casanova

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Schneckenleithner, C., Hoelbl-Kovacic, A., Sexl, V. (2015). Modeling BCR/ABL-Driven Malignancies in the Mouse. In: Eferl, R., Casanova, E. (eds) Mouse Models of Cancer. Methods in Molecular Biology, vol 1267. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2297-0_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2297-0_12

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