Advertisement

Cancer and Metastasis Reviews

, Volume 32, Issue 1–2, pp 63–76 | Cite as

Animal models of leukemia: any closer to the real thing?

  • Guerry J. Cook
  • Timothy S. Pardee
Article

Abstract

Animal models have been invaluable in the efforts to better understand and ultimately treat patients suffering from leukemia. While important insights have been gleaned from these models, limitations must be acknowledged. In this review, we will highlight the various animal models of leukemia and describe their contributions to the improved understanding and treatment of these cancers.

Keywords

Animal model Cancer Leukemia 

Notes

Acknowledgments

The authors would like to acknowledge Karen Klein for help editing the manuscript. Support provided by the Doug Coley Foundation for Leukemia Research, the MacKay Foundation for Cancer Research, the Leight Endowed Research Fund and the Frances P Tutwiler Fund. Additional support to TSP was provided by the National Cancer Institute of the National Institutes of Health under Award Number K08CA169809. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

  1. 1.
    Siegel, R., Ward, E., Brawley, O., & Jemal, A. (2011). Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: A Cancer Journal for Clinicians, 61, 212–236.CrossRefGoogle Scholar
  2. 2.
    Gilliland, D.G., Jordan, C.T., Felix, C.A. (2004). The molecular basis of leukemia. Hematology/the Education Program of the American Society of Hematology, 80–97.Google Scholar
  3. 3.
    Licht, J.D., & Sternberg, D.W. (2005). The molecular pathology of acute myeloid leukemia. Hematology/the Education Program of the American Society of Hematology, 137–142.Google Scholar
  4. 4.
    Lowenberg, B. (2008). Acute myeloid leukemia: the challenge of capturing disease variety. Hematology / the Education Program of the American Society of Hematology, 2008, 1–11.CrossRefGoogle Scholar
  5. 5.
    Dohner, H., Estey, E. H., Amadori, S., et al. (2010). Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood, 115, 453–474.PubMedCrossRefGoogle Scholar
  6. 6.
    Nervi, B., Ramirez, P., Rettig, M. P., et al. (2009). Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood, 113, 6206–6214.PubMedCrossRefGoogle Scholar
  7. 7.
    Jaiswal, S., Jamieson, C. H., Pang, W. W., et al. (2009). CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell, 138, 271–285.PubMedCrossRefGoogle Scholar
  8. 8.
    Majeti, R., Chao, M. P., Alizadeh, A. A., et al. (2009). CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell, 138, 286–299.PubMedCrossRefGoogle Scholar
  9. 9.
    Colmone, A., Amorim, M., Pontier, A. L., Wang, S., Jablonski, E., & Sipkins, D. A. (2008). Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science, 322, 1861–1865.PubMedCrossRefGoogle Scholar
  10. 10.
    Lapidot, T., Sirard, C., Vormoor, J., et al. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367, 645–648.PubMedCrossRefGoogle Scholar
  11. 11.
    Jordan, C. T., Guzman, M. L., & Noble, M. (2006). Cancer stem cells. The New England Journal of Medicine, 355, 1253–1261.PubMedCrossRefGoogle Scholar
  12. 12.
    Skipper, H. E., & Perry, S. (1970). Kinetics of normal and leukemic leukocyte populations and relevance to chemotherapy. Cancer Research, 30, 1883–1897.PubMedGoogle Scholar
  13. 13.
    Law, L. W., Taormina, V., & Boyle, P. J. (1954). Response of acute lymphocytic leukemias to the purine antagonist 6-mercaptopurine. Annals of the New York Academy of Sciences, 60, 244–250.PubMedCrossRefGoogle Scholar
  14. 14.
    McCormack, E., Bruserud, O., & Gjertsen, B. T. (2005). Animal models of acute myelogenous leukaemia—development, application and future perspectives. Leukemia, 19, 687–706.PubMedCrossRefGoogle Scholar
  15. 15.
    Skipper, H. E., Schabel, F. M., Jr., & Wilcox, W. S. (1967). Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells. Cancer Chemotherapy Reports, 51, 125–165.Google Scholar
  16. 16.
    Friend, C. (1957). Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. The Journal of Experimental Medicine, 105, 307–318.PubMedCrossRefGoogle Scholar
  17. 17.
    Linemeyer, D. L., Menke, J. G., Ruscetti, S. K., Evans, L. H., & Scolnick, E. M. (1982). Envelope gene sequences which encode the gp52 protein of spleen focus-forming virus are required for the induction of erythroid cell proliferation. Journal of Virology, 43, 223–233.PubMedGoogle Scholar
  18. 18.
    Wolff, L., & Ruscetti, S. (1985). Malignant transformation of erythroid cells in vivo by introduction of a nonreplicating retrovirus vector. Science, 228, 1549–1552.PubMedCrossRefGoogle Scholar
  19. 19.
    Back, J., Dierich, A., Bronn, C., Kastner, P., & Chan, S. (2004). PU.1 determines the self-renewal capacity of erythroid progenitor cells. Blood, 103, 3615–3623.PubMedCrossRefGoogle Scholar
  20. 20.
    Erkeland, S. J., Valkhof, M., Heijmans-Antonissen, C., et al. (2004). Large-scale identification of disease genes involved in acute myeloid leukemia. Journal of Virology, 78, 1971–1980.PubMedCrossRefGoogle Scholar
  21. 21.
    Caudell, D., Harper, D. P., Novak, R. L., et al. (2010). Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice. Blood, 115, 1194–1203.PubMedCrossRefGoogle Scholar
  22. 22.
    Slape, C., Hartung, H., Lin, Y. W., Bies, J., Wolff, L., & Aplan, P. D. (2007). Retroviral insertional mutagenesis identifies genes that collaborate with NUP98-HOXD13 during leukemic transformation. Cancer Research, 67, 5148–5155.PubMedCrossRefGoogle Scholar
  23. 23.
    Skipper, H. E., Schabel, F. M., Jr., Trader, M. W., & Laster, W. R., Jr. (1969). Response to therapy of spontaneous, first passage, and long passage lines of AK leukemia. Cancer Chemotherapy Reports, 53, 345–366.Google Scholar
  24. 24.
    Vassiliou, G. S., Cooper, J. L., Rad, R., et al. (2011). Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nature Genetics, 43, 470–475.PubMedCrossRefGoogle Scholar
  25. 25.
    Collier, L. S., Adams, D. J., Hackett, C. S., et al. (2009). Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality. Cancer Research, 69, 8429–8437.PubMedCrossRefGoogle Scholar
  26. 26.
    Heyer, J., Kwong, L. N., Lowe, S. W., & Chin, L. (2010). Non-germline genetically engineered mouse models for translational cancer research. Nature Reviews. Cancer, 10, 470–480.PubMedCrossRefGoogle Scholar
  27. 27.
    Early, E., Moore, M. A., Kakizuka, A., et al. (1996). Transgenic expression of PML/RARalpha impairs myelopoiesis. Proceedings of the National Academy of Sciences of the United States of America, 93, 7900–7904.PubMedCrossRefGoogle Scholar
  28. 28.
    Brown, D., Kogan, S., Lagasse, E., et al. (1997). A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 94, 2551–2556.PubMedCrossRefGoogle Scholar
  29. 29.
    Grisolano, J. L., Wesselschmidt, R. L., Pelicci, P. G., & Ley, T. J. (1997). Altered myeloid development and acute leukemia in transgenic mice expressing PML-RAR alpha under control of cathepsin G regulatory sequences. Blood, 89, 376–387.PubMedGoogle Scholar
  30. 30.
    He, L. Z., Guidez, F., Tribioli, C., et al. (1998). Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nature Genetics, 18, 126–135.PubMedCrossRefGoogle Scholar
  31. 31.
    Zuber, J., Radtke, I., Pardee, T. S., et al. (2009). Mouse models of human AML accurately predict chemotherapy response. Genes & Development, 23, 877–889.CrossRefGoogle Scholar
  32. 32.
    Grimwade, D., Walker, H., Oliver, F., et al. (1998). The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood, 92, 2322–2333.PubMedGoogle Scholar
  33. 33.
    Okuda, T., Cai, Z., Yang, S., et al. (1998). Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood, 91, 3134–3143.PubMedGoogle Scholar
  34. 34.
    Rhoades, K. L., Hetherington, C. J., Harakawa, N., et al. (2000). Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood, 96, 2108–2115.PubMedGoogle Scholar
  35. 35.
    Yuan, Y., Zhou, L., Miyamoto, T., et al. (2001). AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proceedings of the National Academy of Sciences of the United States of America, 98, 10398–10403.PubMedCrossRefGoogle Scholar
  36. 36.
    Dash, A. B., Williams, I. R., Kutok, J. L., et al. (2002). A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proceedings of the National Academy of Sciences of the United States of America, 99, 7622–7627.PubMedCrossRefGoogle Scholar
  37. 37.
    Grisolano, J. L., O’Neal, J., Cain, J., & Tomasson, M. H. (2003). An activated receptor tyrosine kinase, TEL/PDGFbetaR, cooperates with AML1/ETO to induce acute myeloid leukemia in mice. Proceedings of the National Academy of Sciences of the United States of America, 100, 9506–9511.PubMedCrossRefGoogle Scholar
  38. 38.
    Lavau, C., Du, C., Thirman, M., & Zeleznik-Le, N. (2000). Chromatin-related properties of CBP fused to MLL generate a myelodysplastic-like syndrome that evolves into myeloid leukemia. EMBO Journal, 19, 4655–4664.PubMedCrossRefGoogle Scholar
  39. 39.
    Look, A. T. (1997). Oncogenic transcription factors in the human acute leukemias. Science, 278, 1059–1064.PubMedCrossRefGoogle Scholar
  40. 40.
    Daser, A., & Rabbitts, T. H. (2004). Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis. Genes & Development, 18, 965–974.CrossRefGoogle Scholar
  41. 41.
    Corral, J., Lavenir, I., Impey, H., et al. (1996). An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell, 85, 853–861.PubMedCrossRefGoogle Scholar
  42. 42.
    Strissel, P. L., Strick, R., Tomek, R. J., Roe, B. A., Rowley, J. D., & Zeleznik-Le, N. J. (2000). DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis. Human Molecular Genetics, 9, 1671–1679.PubMedCrossRefGoogle Scholar
  43. 43.
    Collins, E. C., Pannell, R., Simpson, E. M., Forster, A., & Rabbitts, T. H. (2000). Inter-chromosomal recombination of Mll and Af9 genes mediated by cre-loxP in mouse development. EMBO Reports, 1, 127–132.PubMedCrossRefGoogle Scholar
  44. 44.
    Forster, A., Pannell, R., Drynan, L. F., et al. (2003). Engineering de novo reciprocal chromosomal translocations associated with Mll to replicate primary events of human cancer. Cancer Cell, 3, 449–458.PubMedCrossRefGoogle Scholar
  45. 45.
    Stirewalt, D. L., & Radich, J. P. (2003). The role of FLT3 in haematopoietic malignancies. Nature Reviews. Cancer, 3, 650–665.PubMedCrossRefGoogle Scholar
  46. 46.
    Li, L., Piloto, O., Nguyen, H. B., et al. (2008). Knock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model. Blood, 111, 3849–3858.PubMedCrossRefGoogle Scholar
  47. 47.
    Greenblatt, S., Li, L., Slape, C., et al. (2012). Knock-in of a FLT3/ITD mutation cooperates with a NUP98-HOXD13 fusion to generate acute myeloid leukemia in a mouse model. Blood.Google Scholar
  48. 48.
    Chan, I. T., & Gilliland, D. G. (2004). Oncogenic K-ras in mouse models of myeloproliferative disease and acute myeloid leukemia. Cell Cycle, 3, 536–537.PubMedCrossRefGoogle Scholar
  49. 49.
    MacKenzie, K. L., Dolnikov, A., Millington, M., Shounan, Y., & Symonds, G. (1999). Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice. Blood, 93, 2043–2056.PubMedGoogle Scholar
  50. 50.
    Martelli, A. M., Nyakern, M., Tabellini, G., et al. (2006). Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia, 20, 911–928.PubMedCrossRefGoogle Scholar
  51. 51.
    Yu, H., Li, Y., Gao, C., et al. (2010). Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN. Leukemia, 24, 1077–1080.PubMedCrossRefGoogle Scholar
  52. 52.
    Cutts, B. A., Sjogren, A. K., Andersson, K. M., et al. (2009). Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice. Blood, 114, 3629–3632.PubMedCrossRefGoogle Scholar
  53. 53.
    de Guzman, C. G., Warren, A. J., Zhang, Z., et al. (2002). Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Molecular and Cellular Biology, 22, 5506–5517.PubMedCrossRefGoogle Scholar
  54. 54.
    Pardee, T. S., Zuber, J., & Lowe, S. W. (2011). Flt3-ITD alters chemotherapy response in vitro and in vivo in a p53-dependent manner. Experimental Hematology, 39, 473–485 e474.PubMedCrossRefGoogle Scholar
  55. 55.
    Bruserud, O., Tore, G. B., Brustugun, O. T., et al. (1995). Effects of interleukin 10 on blast cells derived from patients with acute myelogenous leukemia. Leukemia, 9, 1910–1920.PubMedGoogle Scholar
  56. 56.
    Bruserud, O., Gjertsen, B. T., & von Volkman, H. L. (2000). In vitro culture of human acute myelogenous leukemia (AML) cells in serum-free media: studies of native AML blasts and AML cell lines. Journal of Hematotherapy & Stem Cell Research, 9, 923–932.CrossRefGoogle Scholar
  57. 57.
    Nara, N., & Miyamoto, T. (1982). Direct and serial transplantation of human acute myeloid leukaemia into nude mice. British Journal of Cancer, 45, 778–782.PubMedCrossRefGoogle Scholar
  58. 58.
    Sawyers, C. L., Gishizky, M. L., Quan, S., Golde, D. W., & Witte, O. N. (1992). Propagation of human blastic myeloid leukemias in the SCID mouse. Blood, 79, 2089–2098.PubMedGoogle Scholar
  59. 59.
    Ailles, L. E., Gerhard, B., Kawagoe, H., & Hogge, D. E. (1999). Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese diabetic/severe combined immunodeficient mice. Blood, 94, 1761–1772.PubMedGoogle Scholar
  60. 60.
    Wunderlich, M., Chou, F. S., Link, K. A., et al. (2010). AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia, 24, 1785–1788.PubMedCrossRefGoogle Scholar
  61. 61.
    Svejda, J., Kossey, P., Hlavayova, E., & Svec, F. (1958). Histological picture of the transplantable rat leukaemia induced by x-irradiation and methylcholanthrene. Neoplasma, 5, 123–131.PubMedGoogle Scholar
  62. 62.
    Moriuchi, T., Oikawa, T., Kodama, T., Yamaguchi, H., & Kobayashi, H. (1983). Establishment and characterization of a transplantable rat myelomonocytic leukemia. Cancer Research, 43, 5478–5483.PubMedGoogle Scholar
  63. 63.
    Ivankovic, S., & Zeller, W. J. (1974). [Leukemia L 5222 of the rat strain BD IX. An ethylnitrosourea-induced monocytic-myeloic transplantable form for cytochemical and chemotherapeutic studies]. Blut, 28, 288–292.PubMedCrossRefGoogle Scholar
  64. 64.
    Pearson, J. W., Chaparas, S. D., Torgersen, J. A., Perk, K., Chirigos, M. A., & Sher, N. A. (1974). The effect of drug therapy against a histologically defined rat leukemia. Cancer Research, 34, 355–361.PubMedGoogle Scholar
  65. 65.
    Zeller, W. J., Ivankovic, S., & Schmahl, D. (1975). Chemotherapy of the transplantable acute leukemia L5222 in rats. Cancer Research, 35, 1168–1174.PubMedGoogle Scholar
  66. 66.
    Hagenbeek, A., & Martens, A. C. (1983). Efficacy of high-dose cyclophosphamide in combination with total-body irradiation in the treatment of acute myelocytic leukemia: studies in a relevant rat model. Cancer Research, 43, 408–412.PubMedGoogle Scholar
  67. 67.
    Hagenbeek, A., & Martens, A. C. (1980). The pathogenesis of a rat model for human acute myelocytic leukemia. Haematologica, 65, 293–308.PubMedGoogle Scholar
  68. 68.
    van Bekkum, D. W., van Oosterom, P., & Dicke, K. A. (1976). In vitro colony formation of transplantable rat leukemias in comparison with human acute myeloid leukemia. Cancer Research, 36, 941–946.PubMedGoogle Scholar
  69. 69.
    Martens, A. C., van Bekkum, D. W., & Hagenbeek, A. (1990). Minimal residual disease in leukemia: studies in an animal model for acute myelocytic leukemia (BNML). International Journal of Cell Cloning, 8, 27–38.PubMedCrossRefGoogle Scholar
  70. 70.
    Pruvot, B., Jacquel, A., Droin, N., et al. (2011). Leukemic cell xenograft in zebrafish embryo for investigating drug efficacy. Haematologica, 96, 612–616.PubMedCrossRefGoogle Scholar
  71. 71.
    Corkery, D. P., Dellaire, G., & Berman, J. N. (2011). Leukaemia xenotransplantation in zebrafish–chemotherapy response assay in vivo. British Journal of Haematology, 153, 786–789.PubMedCrossRefGoogle Scholar
  72. 72.
    Osman, D., Gobert, V., Ponthan, F., Heidenreich, O., Haenlin, M., & Waltzer, L. (2009). A Drosophila model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO. Proceedings of the National Academy of Sciences of the United States of America, 106, 12043–12048.PubMedCrossRefGoogle Scholar
  73. 73.
    Hunger, S.P., Lu, X., Devidas, M., et al. (2012). Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children’s Oncology Group. Journal of Clinical Oncology.Google Scholar
  74. 74.
    Pear, W. S., Aster, J. C., Scott, M. L., et al. (1996). Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. The Journal of Experimental Medicine, 183, 2283–2291.PubMedCrossRefGoogle Scholar
  75. 75.
    Heisterkamp, N., Jenster, G., ten Hoeve, J., Zovich, D., Pattengale, P. K., & Groffen, J. (1990). Acute leukaemia in bcr/abl transgenic mice. Nature, 344, 251–253.PubMedCrossRefGoogle Scholar
  76. 76.
    Law, L. W., Dunn, T. B., et al. (1949). Observations on the effect of a folic-acid antagonist on transplantable lymphoid leukemias in mice. Journal of the National Cancer Institute, 10, 179–192.PubMedGoogle Scholar
  77. 77.
    Trainer, D. L., & Wheelock, E. F. (1984). Characterization of L5178Y cell phenotypes isolated during progression of the tumor-dormant state in DBA2 mice. Cancer Research, 44, 2897–2906.PubMedGoogle Scholar
  78. 78.
    Nishimura, T., Muto, K., & Tanaka, N. (1978). Drug sensitivity of an adriamycin-resistant mutant subline of mouse lymphoblastoma L5178Y cells. Journal of Antibiotics (Tokyo), 31, 493–495.CrossRefGoogle Scholar
  79. 79.
    Nishimura, T., Suzuki, H., Muto, K., & Tanaka, N. (1979). Mechanism of adriamycin resistance in a subline of mouse lymphoblastoma L5178Y cells. Journal of Antibiotics (Tokyo), 32, 518–522.CrossRefGoogle Scholar
  80. 80.
    Cloyd, M. W., Hartley, J. W., & Rowe, W. P. (1980). Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. The Journal of Experimental Medicine, 151, 542–552.PubMedCrossRefGoogle Scholar
  81. 81.
    Yun, J. P., Behan, J. W., Heisterkamp, N., et al. (2010). Diet-induced obesity accelerates acute lymphoblastic leukemia progression in two murine models. Cancer Prevention Research (Philadelphia, Pa.), 3, 1259–1264.CrossRefGoogle Scholar
  82. 82.
    Weiser, K. C., Liu, B., Hansen, G. M., et al. (2007). Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma. Mammalian Genome, 18, 709–722.PubMedCrossRefGoogle Scholar
  83. 83.
    Dettman, E. J., Simko, S. J., Ayanga, B., et al. (2011). Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors. Oncogene, 30, 2859–2873.PubMedCrossRefGoogle Scholar
  84. 84.
    Groffen, J., Voncken, J. W., Kaartinen, V., Morris, C., & Heisterkamp, N. (1993). Ph-positive leukemia: a transgenic mouse model. Leukemia & Lymphoma, 11(Suppl 1), 19–24.CrossRefGoogle Scholar
  85. 85.
    Reichert, A., Heisterkamp, N., Daley, G. Q., & Groffen, J. (2001). Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336. Blood, 97, 1399–1403.PubMedCrossRefGoogle Scholar
  86. 86.
    Kaur, P., Feldhahn, N., Zhang, B., et al. (2007). Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia. Molecular Cancer, 6, 67.PubMedCrossRefGoogle Scholar
  87. 87.
    Chen, W., Li, Q., Hudson, W. A., Kumar, A., Kirchhof, N., & Kersey, J. H. (2006). A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy. Blood, 108, 669–677.PubMedCrossRefGoogle Scholar
  88. 88.
    Metzler, M., Forster, A., Pannell, R., et al. (2006). A conditional model of MLL-AF4 B-cell tumourigenesis using invertor technology. Oncogene, 25, 3093–3103.PubMedCrossRefGoogle Scholar
  89. 89.
    Tamai, H., Miyake, K., Takatori, M., et al. (2011). Activated K-Ras protein accelerates human MLL/AF4-induced leukemo-lymphomogenicity in a transgenic mouse model. Leukemia, 25, 888–891.PubMedCrossRefGoogle Scholar
  90. 90.
    Harris, A. W., Pinkert, C. A., Crawford, M., Langdon, W. Y., Brinster, R. L., & Adams, J. M. (1988). The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells. The Journal of Experimental Medicine, 167, 353–371.PubMedCrossRefGoogle Scholar
  91. 91.
    Schmitt, C. A., McCurrach, M. E., de Stanchina, E., Wallace-Brodeur, R. R., & Lowe, S. W. (1999). INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes & Development, 13, 2670–2677.CrossRefGoogle Scholar
  92. 92.
    Schmitt, C. A., Fridman, J. S., Yang, M., et al. (2002). A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell, 109, 335–346.PubMedCrossRefGoogle Scholar
  93. 93.
    Grabher, C., von Boehmer, H., & Look, A. T. (2006). Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nature Reviews. Cancer, 6, 347–359.PubMedCrossRefGoogle Scholar
  94. 94.
    Ellisen, L. W., Bird, J., West, D. C., et al. (1991). TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell, 66, 649–661.PubMedCrossRefGoogle Scholar
  95. 95.
    Weng, A. P., Ferrando, A. A., Lee, W., et al. (2004). Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science, 306, 269–271.PubMedCrossRefGoogle Scholar
  96. 96.
    Deftos, M. L., Huang, E., Ojala, E. W., Forbush, K. A., & Bevan, M. J. (2000). Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes. Immunity, 13, 73–84.PubMedCrossRefGoogle Scholar
  97. 97.
    Fowlkes, B. J., & Robey, E. A. (2002). A reassessment of the effect of activated Notch1 on CD4 and CD8 T cell development. Journal of Immunology, 169, 1817–1821.Google Scholar
  98. 98.
    Priceputu, E., Bouallaga, I., Zhang, Y., et al. (2006). Structurally distinct ligand-binding or ligand-independent Notch1 mutants are leukemogenic but affect thymocyte development, apoptosis, and metastasis differently. Journal of Immunology, 177, 2153–2166.Google Scholar
  99. 99.
    Berquam-Vrieze, K. E., Swing, D. A., Tessarollo, L., & Dupuy, A. J. (2012). Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1. Genesis, 50, 112–118.PubMedCrossRefGoogle Scholar
  100. 100.
    Boulos, N., Mulder, H. L., Calabrese, C. R., et al. (2011). Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood, 117, 3585–3595.PubMedCrossRefGoogle Scholar
  101. 101.
    Duy, C., Hurtz, C., Shojaee, S., et al. (2011). BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition. Nature, 473, 384–388.PubMedCrossRefGoogle Scholar
  102. 102.
    Wang, P. Y., Young, F., Chen, C. Y., et al. (2008). The biologic properties of leukemias arising from BCR/ABL-mediated transformation vary as a function of developmental origin and activity of the p19ARF gene. Blood, 112, 4184–4192.PubMedCrossRefGoogle Scholar
  103. 103.
    Barabe, F., Kennedy, J. A., Hope, K. J., & Dick, J. E. (2007). Modeling the initiation and progression of human acute leukemia in mice. Science, 316, 600–604.PubMedCrossRefGoogle Scholar
  104. 104.
    Wei, J., Wunderlich, M., Fox, C., et al. (2008). Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell, 13, 483–495.PubMedCrossRefGoogle Scholar
  105. 105.
    le Viseur, C., Hotfilder, M., Bomken, S., et al. (2008). In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties. Cancer Cell, 14, 47–58.PubMedCrossRefGoogle Scholar
  106. 106.
    Chiu, P. P., Jiang, H., & Dick, J. E. (2010). Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance. Blood, 116, 5268–5279.PubMedCrossRefGoogle Scholar
  107. 107.
    Otova, B., Sladka, M., Panczak, A., & Marinov, I. (1997). Biological characteristics of spontaneous transplantable T-cell lymphomas in inbred Sprague–Dawley/Cub rats. Transplantation Proceedings, 29, 1754–1755.PubMedCrossRefGoogle Scholar
  108. 108.
    Otova, B., Vaclavikova, R., Danielova, V., et al. (2006). Effects of paclitaxel, docetaxel and their combinations on subcutaneous lymphomas in inbred Sprague–Dawley/Cub rats. European Journal of Pharmaceutical Sciences, 29, 442–450.PubMedCrossRefGoogle Scholar
  109. 109.
    Congdon, C. C., & Lorenz, E. (1954). Leukemia in guinea-pigs. American Journal of Pathology, 30, 337–359.PubMedGoogle Scholar
  110. 110.
    Sabaawy, H. E., Azuma, M., Embree, L. J., Tsai, H. J., Starost, M. F., & Hickstein, D. D. (2006). TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 103, 15166–15171.PubMedCrossRefGoogle Scholar
  111. 111.
    Frazer, J. K., Meeker, N. D., Rudner, L., et al. (2009). Heritable T-cell malignancy models established in a zebrafish phenotypic screen. Leukemia, 23, 1825–1835.PubMedCrossRefGoogle Scholar
  112. 112.
    Langenau, D. M., Traver, D., Ferrando, A. A., et al. (2003). Myc-induced T cell leukemia in transgenic zebrafish. Science, 299, 887–890.PubMedCrossRefGoogle Scholar
  113. 113.
    Feng, H., Langenau, D. M., Madge, J. A., et al. (2007). Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish. British Journal of Haematology, 138, 169–175.PubMedCrossRefGoogle Scholar
  114. 114.
    Feng, H., Stachura, D. L., White, R. M., et al. (2010). T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell, 18, 353–366.PubMedCrossRefGoogle Scholar
  115. 115.
    Nowell, P. C., & Hungerford, D. A. (1962). Chromosome studies in human leukemia. IV. Myeloproliferative syndrome and other atypical myeloid disorders. Journal of the National Cancer Institute, 29, 911–931.PubMedGoogle Scholar
  116. 116.
    Goldman, J.M., (2009). Initial treatment for patients with CML. Hematology/the Education Program of the American Society of Hematology, 453–460.Google Scholar
  117. 117.
    Daley, G. Q., Van Etten, R. A., & Baltimore, D. (1990). Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science, 247, 824–830.PubMedCrossRefGoogle Scholar
  118. 118.
    Li, S., Ilaria, R. L., Jr., Million, R. P., Daley, G. Q., & Van Etten, R. A. (1999). The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. The Journal of Experimental Medicine, 189, 1399–1412.PubMedCrossRefGoogle Scholar
  119. 119.
    Zhang, H., Li, H., Xi, H. S., & Li, S. (2012). HIF1alpha is required for survival maintenance of chronic myeloid leukemia stem cells. Blood, 119, 2595–2607.PubMedCrossRefGoogle Scholar
  120. 120.
    Huettner, C. S., Koschmieder, S., Iwasaki, H., et al. (2003). Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. Blood, 102, 3363–3370.PubMedCrossRefGoogle Scholar
  121. 121.
    Huettner, C. S., Zhang, P., Van Etten, R. A., & Tenen, D. G. (2000). Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nature Genetics, 24, 57–60.PubMedCrossRefGoogle Scholar
  122. 122.
    Chu, S., McDonald, T., Lin, A., et al. (2011). Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment. Blood, 118, 5565–5572.PubMedCrossRefGoogle Scholar
  123. 123.
    Lozzio, B. B., Lozzi, C. B., & Machado, E. (1976). Human myelogenous (Ph+) leukemia cell line: transplantation into athymic mice. Journal of the National Cancer Institute, 56, 627–629.PubMedGoogle Scholar
  124. 124.
    Skorski, T., Nieborowska-Skorska, M., Nicolaides, N. C., et al. (1994). Suppression of Philadelphia1 leukemia cell growth in mice by BCR-ABL antisense oligodeoxynucleotide. Proceedings of the National Academy of Sciences of the United States of America, 91, 4504–4508.PubMedCrossRefGoogle Scholar
  125. 125.
    Dazzi, F., Hasserjian, R., Gordon, M. Y., et al. (2000). Normal and chronic phase CML hematopoietic cells repopulate NOD/SCID bone marrow with different kinetics and cell lineage representation. The Hematology Journal, 1, 307–315.PubMedCrossRefGoogle Scholar
  126. 126.
    Dohner, H., Stilgenbauer, S., Benner, A., et al. (2000). Genomic aberrations and survival in chronic lymphocytic leukemia. The New England Journal of Medicine, 343, 1910–1916.PubMedCrossRefGoogle Scholar
  127. 127.
    Phillips, J. A., Mehta, K., Fernandez, C., & Raveche, E. S. (1992). The NZB mouse as a model for chronic lymphocytic leukemia. Cancer Research, 52, 437–443.PubMedGoogle Scholar
  128. 128.
    Raveche, E. S., Salerno, E., Scaglione, B. J., et al. (2007). Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood, 109, 5079–5086.PubMedCrossRefGoogle Scholar
  129. 129.
    Narducci, M. G., Pescarmona, E., Lazzeri, C., et al. (2000). Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. Cancer Research, 60, 2095–2100.PubMedGoogle Scholar
  130. 130.
    Bichi, R., Shinton, S. A., Martin, E. S., et al. (2002). Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proceedings of the National Academy of Sciences of the United States of America, 99, 6955–6960.PubMedCrossRefGoogle Scholar
  131. 131.
    Aguilar-Santelises, M., Rottenberg, M. E., Lewin, N., Mellstedt, H., & Jondal, M. (1996). Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression. International Journal of Cancer, 69, 114–119.CrossRefGoogle Scholar
  132. 132.
    Munzert, G., Kirchner, D., Stobbe, H., et al. (2002). Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis. Blood, 100, 3749–3756.PubMedCrossRefGoogle Scholar
  133. 133.
    Zapata, J. M., Krajewska, M., Morse, H. C., 3rd, Choi, Y., & Reed, J. C. (2004). TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 101, 16600–16605.PubMedCrossRefGoogle Scholar
  134. 134.
    Mohammad, R. M., Mohamed, A. N., Hamdan, M. Y., et al. (1996). Establishment of a human B-CLL xenograft model: utility as a preclinical therapeutic model. Leukemia, 10, 130–137.PubMedGoogle Scholar
  135. 135.
    Mohammad, R. M., Limvarapuss, C., Hamdy, N., et al. (1999). Treatment of a de novo fludarabine resistant-CLL xenograft model with bryostatin 1 followed by fludarabine. International Journal of Oncology, 14, 945–950.PubMedGoogle Scholar
  136. 136.
    Loisel, S., Ster, K. L., Quintin-Roue, I., et al. (2005). Establishment of a novel human B-CLL-like xenograft model in nude mouse. Leukemia Research, 29, 1347–1352.PubMedCrossRefGoogle Scholar
  137. 137.
    Durig, J., Ebeling, P., Grabellus, F., et al. (2007). A novel nonobese diabetic/severe combined immunodeficient xenograft model for chronic lymphocytic leukemia reflects important clinical characteristics of the disease. Cancer Research, 67, 8653–8661.PubMedCrossRefGoogle Scholar
  138. 138.
    Aydin, S., Grabellus, F., Eisele, L., et al. (2011). Investigating the role of CD38 and functionally related molecular risk factors in the CLL NOD/SCID xenograft model. European Journal of Haematology, 87, 10–19.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Section on Hematology and OncologyWake Forest Baptist HealthWinston-SalemUSA

Personalised recommendations