Glucocorticoids induce apoptosis in acute myeloid leukemia cell lines with A t(8;21) chromosome translocation.
The t(8;21) chromosome translocation frequently occurs in the AML, acute myeloid leukemia, M2 sub-type. This translocation juxtaposes the AML1 gene on chromosome 21 with the MTG8(ETO) gene on chromosome 8, resulting in the expression of the AML1-MTG8(ETO) fusion transcript. The fusion product is thought to play a critical role in the abnormal proliferation and differentiation of myeloid leukemia cells. We investigated the effects of various differentiation inducers of myeloid leukemia cells on the growth and differentiation of Kasumi-1 and SKNO-1 cells, AML cell lines with t(8;21). These cells resisted differentiation into mature granulocytes and macrophages in response to various inducers of myelomonocytic differentiation, such as dimethyl sulfoxide, retinoic acid, butyrate, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1alpha,25-dihydroxyvitamin D3. On the other hand, dexamethasone can induce apoptosis in these cells at low concentrations, whereas other myelomonocytic leukemia cell lines tested were resistant to glucocorticoid-induced apoptosis. The levels of glucocorticoid receptor gene expression were high in Kasumi-1 and SKNO-1 cells. Expression of the AML1-MTG8(ETO), bcl-2, and c-myc genes was unchanged following exposure to dexamethasone. Glucocorticoids might induce the apoptosis of some types of AML cells, just like that of some lymphoid leukemia cells.
Miyoshi
H
H
National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Ohki
M
M
Nakagawa
T
T
Honma
Y
Y
D000208:Acute Disease; D017209:Apoptosis; D002454:Cell Differentiation; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D003907:Dexamethasone