The M4Eo subtype of acute myeloid leukemia (AML) is a variant characterized by an increased number of morphologically abnormal eosinophils in bone marrow and peripheral blood, in addition to the accumulation of immature blasts common to all acute leukemias (Bennett et al. 1985). It constitutes about 8% of AML (Mitelman and Heim 1992). The leukemic cells of most M4Eo patients are characterized by a pericentric inversion of chromosome 16 (inv [16][p13; q22])(Arthur and Bloomfield 1983; Le Beau et al. 1983), although other chromosome 16 abnormalities involving p13 and q22, eg, t (16; 16)(p13; q22), are also occasionally seen (Hogge et al. 1984; Testa et al. 1984; Holmes et al. 1985; Larson et al. 1986). Given the absence of other karyotypic abnormalities in many of these patients, a pathogenic relationship between inversion 16 and the M4Eo leukemia has been suggested.

Through positional cloning, we recently cloned both the long-and short-arm chromosome breakpoints of inv (16), and identified the genes directly involved. The gene located at the q arm breakpoint is CBFB, a human homolog of the mouse transcription factor PEBP2/CBFfl which, in combination with CBFa, binds to specific DNA sequences and regulates expression of a number of genes transcribed in hematopoietic cells. A smooth muscle myosin heavy-chain gene (MYHll) was found at the p arm breakpoint. We demonstrated that a fusion transcript is generated in the leukemic cells between the CBFB gene on 16q and MYHll on 16p (Liu et al. 1993a, b).