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Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a)

Leukemia volume 18, pages 538–547 (2004)Cite this article

Abstract

Chronic myeloid leukemia (CML) is characterized by the expression of the P210 BCR/ABL fusion protein. The molecular mechanisms behind this oncogene-mediated hematological disease are, however, not fully understood. Here, we describe the establishment and phenotypic characterization of U937 cells in which P210 BCR/ABL can be conditionally expressed using tetracycline. The induction of BCR/ABL in the obtained clones resulted in a rapid phosphorylation of the STAT1, STAT3 and STAT5 molecules, consistent with the findings in other model systems. Phenotypic characterization of the clones revealed that BCR/ABL induces a slight decrease in the proliferation and viability, without a marked effect on cell cycle distribution, the rate of apoptosis or on cellular differentiation, as judged by several cell surface markers and capacity to reduce nitro blue tetrazolium. Interestingly, BCR/ABL was found to upregulate the expression of carcinoembryonic-related antigen (CEA)CAM1 (CD66a), which is a plasma membrane-linked glycoprotein belonging to the CEAs and involved in signal transduction and cellular adhesion. The expression of CEACAM1 was reversible upon imatinib treatment in BCR/ABL-expressing U937 cells as well as in BCR/ABL-positive K562 cells. The established cell lines may prove useful in further modeling and dissection of BCR/ABL-induced leukemogenesis.

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Acknowledgements

We thank Drs J Groffen and N Heisterkamp (Childrens Hospital Los Angeles, Los Angeles, CA, USA) for providing AB1/pCDE, Dr GR Adolf (Ernst Boehringer Institut, Vienna, Austria) for supplying human TNFα and Dr E Buchdunger (Novartis, Basel, Switzerland) for providing imatinib mesylate. In addition, we thank H Svedberg (Department of Hematology, Lund University, Lund, Sweden) for help with the NBT reduction test and J Almkvist (Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden) for technical assistance with the antibodies against CEAs used for Western blot analysis. This study was supported by grants from the Swedish Cancer Society and the Swedish Children's Cancer Foundation.

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  1. Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    P Håkansson, C Lassen & T Fioretos

  2. Department of Hematology, Lund University Hospital, Lund, Sweden

    T Olofsson & U Gullberg

  3. Department of Oncology, Lund University Hospital, Lund, Sweden

    B Baldetorp

  4. Department of Rheumatology and Inflammation Research, Phagocyte Research Laboratory, Göteborg University, Göteborg, Sweden

    A Karlsson

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  1. P Håkansson
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Correspondence to P Håkansson.

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Håkansson, P., Lassen, C., Olofsson, T. et al. Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a). Leukemia 18, 538–547 (2004). https://doi.org/10.1038/sj.leu.2403255

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