title: 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.
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.
authors.affiliation: Department of Pediatrics, Yamanashi Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inukai
authors.forename: K
authors.initials: K
authors.lastname: Sugita
authors.forename: K
authors.initials: K
authors.lastname: Mitsui
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.forename: K
authors.initials: K
authors.lastname: Goi
authors.forename: T
authors.initials: T
authors.lastname: Tezuka
authors.forename: S
authors.initials: S
authors.lastname: Kojika
authors.forename: K
authors.initials: K
authors.lastname: Kagami
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Okazaki-Koyama
authors.forename: S
authors.initials: S
authors.lastname: Nakazawa
mesh_terms: D001752:Blast Crisis / Q000473:pathology*; D002455:Cell Division / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor