Cloning of several species of MLL/MEN chimeric cDNAs in myeloid leukemia with t(11;19)(q23;p13.1) translocation

The t(11;19)(q23;p13.1) translocation is thought to play an important role in pathogenesis of myeloid leukemias in older patients. The MLL gene involved in other 11q23 abnormalities was also rearranged by this translocation. Screening of cDNA libraries of the t(11;19)(q23;p13.1)-carrying leukemic cells resulted in the isolation of several species of fusion cDNAs between the MLL gene and an unknown gene on 19p13.1, named MEN (myeloid eleven-nineteen translocation), which is ubiquitously expressed. Although the MLL gene was alternatively spliced, the fusion protein should contain an N-terminal half of the MLL, including AT hook motifs, that is fused to the MEN protein with a lysine-rich sequence, suggesting that the MLL/MEN fusion protein could be a chimeric transcription factor. The MLL/MEN fusion transcripts of 8.0 kb were detected in leukemic cells of two cases with the translocation. The MLL/MEN fusion was consistent in all three cases of the t(11;19)(q23;p13.1)-carrying leukemia examined by RNA-based polymerase chain reaction. These findings strongly suggest that the t(11;19)(q23;p13.1) results in the fusion formation encoding a new class of potential chimeric transcription factor that contributes to leukemogenesis of myeloid lineage.