P. Liu et al., FUSION BETWEEN TRANSCRIPTION FACTOR CBF-BETA PEBP2-BETA AND A MYOSIN HEAVY-CHAIN IN ACUTE MYELOID-LEUKEMIA/, Science, 261(5124), 1993, pp. 1041-1044
The pericentric inversion of chromosome 16 [inv(16)(p13q22)] is a char
acteristic karyotypic abnormality associated with acute myeloid leukem
ia, most commonly of the M4Eo subtype. The 16p and 16q breakpoints wer
e pinpointed by yeast artificial chromosome and cosmid cloning, and th
e two genes involved in this inversion were identified. On 16q the inv
ersion occurred near the end of the coding region for CBFbeta, also kn
own as PEBP2beta, a subunit of a heterodimeric transcription factor re
gulating genes expressed in T cells; on 16p a smooth muscle myosin hea
vy chain (SMMHC) gene (MYH11) was interrupted. In six of six inv(16) p
atient samples tested, an in-frame fusion messenger RNA was demonstrat
ed that connected the first 165 amino acids of CBFbeta with the tail r
egion of SMMHC. The repeated coiled coil of SMMHC may result in dimeri
zation of the CBFbeta fusion protein, which in turn would lead to alte
rations in transcriptional regulation and contribute to leukemic trans
formation.