Structure and expression pattern of a human MTG8/ETO family gene, MTGR1

AML1-MTG8 fusion protein, which is produced from the rearranged gene formed between AML1 and MTG8 in myeloid leukemia with t(8;21) chromosomal translo cation, plays an important role in the pathogenesis of leukemia. We previou sly showed that ectopically expressed AML1-MTG8 fusion protein is associate d with an MTG8-like protein in the mouse myeloid precursor cell line L-G, a nd this association seemed to be required for AML1-MTG8 to stimulate prolif eration. As a candidate cDNA for this MTG8-like protein, a 6.4 kb MTGR1 cDN A encoding human MTGR1b protein of 604 amino acids was isolated. Since this cDNA was shorter than the main mRNA (about 7.5 kb), the 5'-end of the MTGR 1 cDNA was extended using Marathon Ready cDNA. When the newly obtained 5'-s equence was combined with the previous cDNA, the resultant MTGR1 cDNA (6995 bp), including exon 3 that the previous cDNA lacked, could encode MTGR1a p rotein of 575 amino acids. Transcripts of the MTGR1 gene were expressed ubi quitously in the human tissues and cell lines examined. PCR analyses of the cDNAs from human tissues showed the presence of various splicing Variants with regard to the 5'-region including exons 1, 2 and 3. The MTGR1 gene con sists of 14 exons and spans about 68 kb. The genomic structure of MTGR1 is highly similar to those of other MTG 8-family genes, MTG8 and MTG16. MTG16 was recently cloned from the translocation breakpoint of myeloid malignanci es with t(16;21) chromosomal translocation. (C) 2000 Elsevier Science B.V. All rights reserved.