FUSION BETWEEN TRANSCRIPTION FACTOR CBF-BETA PEBP2-BETA AND A MYOSIN HEAVY-CHAIN IN ACUTE MYELOID-LEUKEMIA/

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.