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The Partner Gene of AML1 in t(16;21) Myeloid Malignancies Is a
Novel Member of the MTG8(ETO) Family
Toshie Gamou,
Eiko Kitamura,
Fumie Hosoda,
Kimiko Shimizu,
Kenji Shinohara,
Yasuhide Hayashi,
Takahiro Nagase,
Yasunobu Yokoyama, and
Misao Ohki
From the Radiobiology Division, National Cancer Center Research
Institute, Tokyo; Division of Hematology, Department of Medicine,
Yamaguchi Prefecture Central Hospital, Yamaguchi; Department of
Pediatrics, Faculty of Medicine, University of Tokyo, Tokyo; Kazusa DNA
Research Institute, Chiba; and the Center for Molecular Biology and
Cytogenetics, SRL, Inc, Tokyo, Japan.
The t(16;21)(q24;q22) translocation is a rare but recurrent
chromosomal abnormality associated with therapy-related myeloid malignancies and a variant of the t(8;21) translocation in which the
AML1 gene on chromosome 21 is rearranged. Here we report the molecular definition of this chromosomal aberration in four patients. We cloned cDNAs from the leukemic cells of a patient carrying t(16;21)
by the reverse transcription polymerase chain reaction using an
AML1-specific primer. The structural 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 using
MTG16 probes mainly detected 4.5 kb and 4.2 kb RNAs, along with
several other minor RNAs in various human tissues. As in t(8;21), the t(16;21) breakpoints occurred between the exons 5 and 6 of
AML1, and between 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 fusion in t(16;21)
leukemia results in the production of a protein that is very similar to
the AML1-MTG8 chimeric protein.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4028-4037
© 1998 by The American Society of Hematology.
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