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Participation of granulocyte colony-stimulating factor in the growth regulation of leukemia cells from Philadelphia chromosome-positive acute leukemia and blast crisis of chronic myeloid leukemia

Leukemia volume 14, pages 1386–1395 (2000)Cite this article

Abstract

Granulocyte colony-stimulating factor (G-CSF) has been shown to support the growth of multipotential hematopoietic stem cells in addition to the cells of neutrophilic lineage. Philadelphia chromosome (Ph1)-positive leukemia has its origin in the hematopoietic stem cell. In the present study, we demonstrated that the proliferation of leukemic cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph1-positive acute lymphoblastic leukemia (ALL) cases is frequently stimulated with G-CSF in vitro. We next studied a total of 12 leukemic cell lines established from CML-BC (n = 6) and Ph1-positive acute leukemia (n = 6): four ‘myeloid’, five ‘biphenotypic’, and three ‘lymphoid’ types. All cell lines expressed G-CSF receptor (G-CSFR) in flow cytometric analysis, but their proliferative response to G-CSF in 3H-thymidine incorporation assay varied. The ‘biphenotypic’ cell lines expressed G-CSFR at higher levels and showed the most pronounced response to G-CSF. The ‘lymphoid’ cell lines showed intermediate G-CSFR expression with the modest response to G-CSF. Unexpectedly, ‘myeloid’ cell lines showed lower G-CSFR expression and lower G-CSF response compared with ‘biphenotypic’ cell lines. In three of four ‘myeloid’ cell lines, proliferation was partially inhibited by an addition of anti-G-CSF neutralizing monoclonal antibody into culture medium. Further, the % inhibition of 3H-thymidine uptake of cell lines positively correlated with the amount of their intracellular G-CSF measured by enzyme immunoassay, suggesting an autocrine growth mechanism via the G-CSF/G-CSFR interaction. These results suggest that G-CSF play an important role in the growth regulation of leukemia cells from Ph1-positive acute leukemia and CML-BC.

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Acknowledgements

We thank Kris Dittmer for critical reading of the manuscript, and Chugai Pharmaceutical (Tokyo, Japan) for measuring the intracellular G-CSF.

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Authors and Affiliations

  1. Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan

    T Inukai, K Sugita, K Iijima, K Goi, T Tezuka, S Kojika, K Kagami & S Nakazawa

  2. Second Department of Biochemistry, Yamanashi Medical University, Yamanashi, Japan

    K Mitsui

  3. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

    T Mori, A Kinoshita & T Suzuki

  4. Laboratory of Immunology, Saitama Central Hospital, Saitama, Japan

    T Mori, T Suzuki & T Okazaki-Koyama

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Inukai, T., Sugita, K., Mitsui, K. et al. Participation of granulocyte colony-stimulating factor in the growth regulation of leukemia cells from Philadelphia chromosome-positive acute leukemia and blast crisis of chronic myeloid leukemia. Leukemia 14, 1386–1395 (2000). https://doi.org/10.1038/sj.leu.2401837

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