ALTERATION OF NM23 GENE-EXPRESSION DURING THE INDUCED-DIFFERENTIATIONOF HUMAN LEUKEMIA-CELL LINES

The nm23-H1 gene is regarded as a human homologue of the mouse nm23 ge ne, which was expressed in a nonmetastatic subline of mouse melanoma K -1735. The expression levels of nm23-H1 mRNA and the levels of protein during induced differentiation of human leukemia cell lines were anal ysed. mRNA levels of the megakaryoblastic leukemia line MEG-O1, which were induced to differentiate into megakaryocyte by TPA, decreased rap idly from 2 days after the start of treatment and became almost undete ctable at day 4. Similar downregulation of nm23-H1 mRNA was also obser ved in the induced differentiation of the promyelocytic leukemia line HL-60 by TPA, or DMSO into monocyte-macrophage lineage or granulocytes , respectively. The amount of Nm23-H1 protein was analysed by Western immune-blot analysis using mouse antiserum raised against a recombinan t fusion protein with glutathione S-transferase. The amount of Nm23-H1 protein also decreased during the induced differentiation of these le ukemia cell lines. On the other hand, in the differentiation of the er ythroleukemia line K562 by hemin, levels of both mRNA and protein of N m23-H1 elevated transiently, then reduced to the original level. When MEG-01 and K562 were stably transfected with nm23-H1 cDNA, MEG-O1 tran sfectants showed reduced sensitivity to the induction of differentiati on, whereas K562 transfectants were better induced to synthesize hemog lobin than controls. These findings suggest the possibility that Nm23- H1 protein plays an important role to maintain the proliferation of im mature leukemic cells in MEG-O1 and HL-60, but it may also play a role in the early stage of K562 differentiation, possibly in the different manner.