Interactions between retinoic acid and colony-stimulating factors affecting the blast cells of acute myeloblastic leukemia.
The responses to retinoic acid (RA) of acute myeloblastic leukemia (AML) blasts and normal hemopoietic progenitors was examined under defined growth factor conditions. For the leukemic cells marked patient to patient variation was seen; blast colony formation by cells from some patients was stimulated by RA without growth factors or in the presence of recombinant granulocyte colony-simulating factor (rG-CSF), recombinant granulocyte-macrophage-CSF rGM-CSF and recombinant interleukin-3 (rIL-3); for other populations inhibition was observed under the same conditions. Some blast cells were stimulated by RA in the presence of rGM-CSF and rIL-3 and inhibited when cultured with RA and rG-CSF. Supernatants prepared from blasts cultured with RA and growth factors did not show activities that were not readily explained by the carry-over of growth factors; this result did not provide evidence that RA and growth factors interact to produce factors. Titrations of RA showed that activity was first observed at concentrations of 10(-9) M and was maximum at concentrations of 10(-7) M. Different effects of RA in combination with rG-CSF compared with rGM-CSF or IL-3 were not seen when the cells were tested in suspension culture rather than in methylcellulose, a finding that may be interpreted to mean that the interaction between RA and factors affects terminally-dividing blast cells. Three normal bone marrow samples were cultured with RA and growth factors. Colony formation was stimulated by RA in the presence of rGM-CSF or rIL-3 but inhibited by RA with rG-CSF. Thus a differential effect of RA in combination with growth factors occurs in normal hemopoietic cells and persists in some AML populations.
Tohda
S
S
Ontario Cancer Institute, University of Toronto, Canada.
Minden
M D
MD
McCulloch
E A
EA
D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008747:Methylcellulose; D014212:Tretinoin / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D003470:Culture Media; D014212:Tretinoin; D008747:Methylcellulose