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

T. Inukai, K. Sugita, K. Mitsui, K. Iijima, K. Goi, T. Tezuka, S. Kojika, K. Kagami, T. Mori, A. Kinoshita, T. Suzuki, T. Okazaki-Koyama, S. Nakazawa

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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.

Original languageEnglish
Pages (from-to)1386-1395
Number of pages10
JournalLeukemia
Volume14
Issue number8
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • Autocrine stimulation
  • G-CSF
  • G-CSF production
  • G-CSFR
  • Ph1-positive leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Inukai, T., Sugita, K., Mitsui, K., Iijima, K., Goi, K., Tezuka, T., Kojika, S., Kagami, K., Mori, T., Kinoshita, A., Suzuki, T., Okazaki-Koyama, T., & Nakazawa, S. (2000). 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(8), 1386-1395. https://doi.org/10.1038/sj.leu.2401837