EXPRESSION OF A GENE ENCODING A TRANSFER-RNA SYNTHETASE-LIKE PROTEIN IS ENHANCED IN TUMORIGENIC HUMAN MYELOID-LEUKEMIA CELLS AND IS CELL-CYCLE STAGE-DEPENDENT AND DIFFERENTIATION-DEPENDENT

We cloned a tumorigenic phenotype-associated cDNA encoding a tRNA synt hetase-like protein from an acute-phase human myeloid leukemia cell li ne. The cDNA was isolated by reiterative subtraction of cDNAs synthesi zed from tumor-generating parental leukemia cells versus those from a nontumorigenic variant of the same cells, The selected cDNA encodes a protein that is a close homolog of one subunit of prokaryote and yeast phenylalanyl-tRNA synthetase (PheRS). The expressed protein reacts sp ecificially with polyclonal antibodies raised against mammalian phenyl alanyl-tRNA synthetase. Expression of the gene (designated CML33) was directly confirmed by Northern blot hybridization to be substantially enhanced in the tumorigenic cells compared with the nontumorigenic var iant. In addition, expression of CML33 in myeloid leukemia cells was s ensitive to the stage of the cell cycle and to induction of differenti ation. Although the relationship between these observations and the tu morigenic state of the human myeloid leukemia cell line used in these studies is unknown, to our knowledge, this is the first demonstration in mammalian cells of tumor-selective and cell cycle stage- and differ entiation-dependent expression of a member of the tRNA synthetase gene family.