title: Potentiated maturation with a high proliferating activity of acute promyelocytic leukemia induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors in combination with all-trans retinoic acid.
abstract: All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemia (APL), but the effect of cytokines regulating myeloid differentiation on ATRA-induced APL cells is poorly understood. In this study, maturation and proliferation of fresh APL cells were examined when induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors (G-CSF or GM-CSF) in combination with ATRA. APL cells showed a low proliferating activity when induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed increased DNA syntheses, the levels of which were not significantly affected by the combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF potentiated the capability of ATRA-induced cells to reduce nitroblue tetrazolium (NBT), while G-CSF or GM-CSF alone induced no NBT reduction. Furthermore, in several patients examined, APL cells induced by ATRA with G-CSF showed an increased activity of chemotaxis and CD11a expression. These findings suggest that G-CSF or GM-CSF can potentiate differentiation of ATRA-induced APL cells while stimulating their proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a useful adjunct to promote ATRA-induced differentiation of APL.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Imaizumi
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Koizumi
authors.forename: S
authors.initials: S
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Suwabe
authors.forename: M
authors.initials: M
authors.lastname: Yoshinari
authors.forename: R
authors.initials: R
authors.lastname: Ichinohasama
authors.forename: K
authors.initials: K
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Sawai
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D002675:Child, Preschool; D003561:Cytarabine / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012074:Remission Induction; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor