AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells.
AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages, because a significant level of the AML1 gene is expressed in these cells. We overexpressed AML1a (without the transcription-activating domain) and AML1b (with the domain) proteins in K562 leukemia cells, which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes. The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers, such as hemin, 1-beta-D-arabinofuranosylcytosine, and herbimycin A. The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate. On the other hand, AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone. AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester. These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation.
Niitsu
N
N
Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina, Japan.
Yamamoto-Yamaguchi
Y
Y
Miyoshi
H
H
Shimizu
K
K
Ohki
M
M
Umeda
M
M
Honma
Y
Y
D015703:Antigens, CD / Q000378:metabolism; D002087:Butyrates / Q000037:antagonists & inhibitors*; D020148:Butyric Acid; D002454:Cell Differentiation; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D004900:Erythroblasts / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D008533:Megakaryocytes / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D002087:Butyrates; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D006021:Glycophorins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C493728:RUNX1 protein, human; D014157:Transcription Factors; D020148:Butyric Acid; D013755:Tetradecanoylphorbol Acetate