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

Masue Imaizumi, Atsushi Sato, Yoshitsugu Koizumi, Shigeo Inoue, Hoshiro Suzuki, Naruyoshi Suwabe, Miyako Yoshinari, Ryo Ichinohasama, Kazuyasu Endo, Takashi Sawai, Keiya Tada

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22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1301-1308
Number of pages8
JournalLeukemia
Volume8
Issue number8
Publication statusPublished - 1994 Aug

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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