T. Gamou et al., THE PARTNER GENE OF AML1 IN T(16-21) MYELOID MALIGNANCIES IS A NOVEL MEMBER OF THE MTG8(ETO) FAMILY, Blood, 91(11), 1998, pp. 4028-4037
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.