Collaboration of PIM-1 and BCL-2 in Lymphomagenesis (original) (raw)

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Previously, We Have Shown That Pim-1 Transgenic Mice Are Predisposed To Lymphomagenesis. Although The Spontaneous Tumor Incidence In Pim-1 Transgenic Mice Is Extremely Low, Tumor Induction By Carcinogens (Breuer Et Al., 1989; 1991) Or Murine Leukemia Virus Infection (Van Lohuizen Et Al., 1989) Showed A Dramatic Acceleration Of Disease In The Transgenic Mice As Compared To Nontransgenic Littermates. Either The Proto-Oncogenes C-Myc Or N-Myc Were Found To Be Activated In The Mulv-Induced T-Cell Lymphomas In Pim-1 Transgenic Mice, Whereas Activation Of Myc By Proviral Insertion Was Only Found In A Fraction Of The Lymphomas Induced In Nontransgenic Littermates. This Suggested That Pim-1 And Myc Were Efficient Collaborators In Mulv-Induced T-Cell Lymphomas. Support For The Strong Synergistic Interaction Between Pim-1 And Myc Came Also From Mulv-Induced Tumor Acceleration Studies In Eμ-Myc Transgenic Mice. Here Activation Of The Pim-1 Proto-Oncogene Was Frequently Found In Pre-B Cell Lymphomas (Van Lohuizen Et Al., 1991). This Was Further Substantiated In Crossbreeding Experiments Without The Use Of Any Tumor-Accelerating Agent: Double Transgenic Mice Carrying Both An Activated Pim-1 And C-Myc Oncogene Died In Utero From Lymphoblastic Leukemia (Verbeek Et Al., 1991). The Phenotype Of Crosses Between Pim-1 And Either N-Myc Or L-Myc Was Somewhat Less Severe, In Agreement With The Reduced Oncogenicity Of The Myc Oncogenes In The Order C-Myc < N-Myc < L-Myc As Was Observed In Cell Culture (MöRöY Et Al., 1991). Transplantation Of Leukemic Cells From Double Transgenic Embryos Carrying The Pim-1 And C-Myc Oncogenes Indicated That Additional Events Were Involved In The Progression Of These Tumors To Full Malignancy. Mulv Infection Of Eμ-Myc And Eμ-Pim-1 Transgenic Mice Has Uncovered A Number Of New Genes That Collaborate With Myc And Pim-1 In Transformation. These Encompass Bmi-1, Pal-1 (Van Lohuizen Et Al., 1991) And Others Which Are Currently Being Identified (Jonkers & Berns, Unpublished Results). However, Other Oncogenes That Can Contribute To These Tumor Types, Such As Myb, Abl, And Bcl-2 Appeared Not To Be Involved. We Were Particularly Intrigued By The Lack Of Involvement Of Bcl-2, Which Was Previously Shown To Collaborate With C-Myc In Vitro (Vaux Et Al., 1988) And In Vivo. Evidence For Collaboration Between C-Myc And Bcl-2 In Vivo Came From The Presence Of C-Myc Rearrangements In Immunoblastic Lymphomas That Spontaneously Developed In Bcl-2-Lg Mice (Mcdonnell Et Al., 1991). Additional support came from crossbreeding of Eμ-myc and Eμ-bcl 2: A high incidence of primitive lymphoid tumors was found in double transgenic mice (Strasser et al., 1990). Here we report on the interaction of pim-1 and bcl-2 in crosses between pim-1 and bcl-2 transgenic mice and on the MuLV-induced tumorigenesis in these mice.

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Authors and Affiliations

1. Division of Molecular Genetics, the Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands
   D. Acton, J. Domen, H. Jacobs, M. Vlaar & A. Berns
2. The Howard Hughes Medical Institute and the Department of Medicine and Molecular Microbiology, Washington University School of Medicine, 660 South Euclid, St. Louis, Missouri, 63110, USA
   S. Korsmeyer

Authors

1. D. Acton
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2. J. Domen
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3. H. Jacobs
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4. M. Vlaar
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5. S. Korsmeyer
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6. A. Berns
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Editors and Affiliations

1. Laboratory of Genetics, National Cancer Institute National Institutes of Health, Bldg. 37, Rm 2B04, Bethesda, MD, 20892, USA
   Michael Potter M. D (Chief) (Chief)
2. Institute for Immunology, Grenzacherstr. 487, CH-4005, Basel, Switzerland
   Fritz Melchers (Director) (Director)

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© 1992 Springer-Verlag Berlin Heidelberg

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Acton, D., Domen, J., Jacobs, H., Vlaar, M., Korsmeyer, S., Berns, A. (1992). Collaboration of PIM-1 and BCL-2 in Lymphomagenesis. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1992. Current Topics in Microbiology and Immunology, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77633-5\_36

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• DOI: https://doi.org/10.1007/978-3-642-77633-5\_36
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