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

Leukemia. 2004 Mar;18(3):538-47. doi: 10.1038/sj.leu.2403255.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Antigens, Differentiation / metabolism*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Benzamides
  • Carcinoembryonic Antigen / metabolism
  • Cell Adhesion Molecules
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • DNA-Binding Proteins / metabolism
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Milk Proteins*
  • Phenotype
  • Piperazines / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / pharmacology
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Trans-Activators / metabolism
  • Transfection
  • U937 Cells
  • Up-Regulation

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Antineoplastic Agents
  • Benzamides
  • CD66 antigens
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • Milk Proteins
  • Piperazines
  • Pyrimidines
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT5 Transcription Factor
  • Trans-Activators
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl