Effects of retinoic acid on a new human erythromegakaryocytic cell line AP-217.
We have characterized a new human cell line AP-217, derived from the peripheral blood of a patient with chronic myeloid leukemia in blastic crisis. The analysis of cell surface antigens and ploidy showed that AP-217 was an erythro-megakaryocytic cell line. The effects of inducers of differentiation were studied and focused on retinoic acid (RA). Uninduced AP-217 cells produced a low level of hemoglobin (Hb) that showed a moderate but significant dose-dependent increase after 13 cis-RA induction (four times above the control at 10(-5) M). To outline this effect, AP-217 cells were cloned at limiting dilution. A subclone (clone 2) was isolated which expressed glycophorin A on 12% of cells, and showed a marked sensitivity to RA. After a 4 day induction with increasing concentrations of RA (1-10 x 10(-6) M) Hb production by clone 2 cells was enhanced 12 times over the control at the highest concentration (10(-5) M). No effect of RA on the Hb production of K-562 and HEL was observed. This increased Hb production occurred simultaneously with a growth inhibition in clonogenic cultures (20% reduction) associated with a drastic reduction of the colony size. Moreover, we demonstrated the expression of mRNA for the beta globin gene in clone 2 and AP-217-cells. This is the first report of a positive effect of RA on the erythroid differentiation of a human leukemic cell line.
Mossuz
P
P
Laboratoire d'Hématologie, CHU A.Michallon, Grenoble, France.
Prandini
M H
MH
Leroux
D
D
Valiron
O
O
Schweitzer
A
A
Sassetti
B
B
Kolodie
L
L
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005914:Globins / Q000235:genetics; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D006454:Hemoglobins; D005914:Globins; D015474:Isotretinoin