THE PARTNER GENE OF AML1 IN T(16-21) MYELOID MALIGNANCIES IS A NOVEL MEMBER OF THE MTG8(ETO) FAMILY

The t(16;21)(q24;q22) translocation is a rare but recurrent chromosoma l abnormality associated with therapy-related myeloid malignancies and a variant of the t(8;21) translocation in which the AML1 gene on chro mosome 21 is rearranged. Here we report the molecular definition of th is chromosomal aberration in four patients. We cloned cDNAs from the l eukemic cells of a patient carrying t(16;21) by the reverse transcript ion polymerase chain reaction using an AML1-specific primer. The struc tural analysis of the cDNAs showed that AML1 was fused to a novel gene named MTG16 (Myeloid Translocation Gene on chromosome 16) which shows high homology to MTG8 (ETO/CDR) and MTGR1. Northern blot analysis usi ng MTG16 probes mainly detected 4.5 kb and 4.2 kb RNAs, along with sev eral other minor RNAs in various human tissues. As in t(8;21), the t(1 6:21) breakpoints occurred between the exons 5 and 6 of AML1, and betw een the exons 1 and 2 or the exons 3 and 4 of MTG16. The two genes are fused in-frame, resulting in the characteristic chimeric transcripts of this translocation. Although the reciprocal chimeric product, MTG16 -AML1, was also detected in one of the t(16;21) patients, its protein product was predicted to be truncated. Thus, the AML1-MTG16 gene fusio n in t(16;21) leukemia results in the production of a protein that is very similar to the AML1-MTG8 chimeric protein. (C) 1998 by The Americ an Society of Hematology.