Molecular identification of a new splicing variant of the MLL-MLLT11 fusion transcript in an adult with acute myeloid leukemia and t(1;11)(q21;q23)

摘要

More than 70 different mixed lineage leukemia (MLL) rearrangements involving 11q23 have been molecularly characterized in acute leukemia. Among these, the MLLT11 gene is highly unique as MLL fusion partner because the entire open reading frame is usually fused in-frame to the N-terminal portion of the MLL gene. By using molecular genetic methods, we identified the chromosomal fusion site within MLL exon 10 sequences which were fused to the MLLT11 intron 1 sequences. This unusual break site results in the creation of two in-frame MLL-MLLT11 fusion transcripts in this acute myeloid leukemia patient with t(1;11)(q21;q23). One fusion transcript represents a normal splice product, while the other contains intronic sequences and a cryptic splice event in order to generate an intact fusion transcript. We also reviewed all published articles which have reported t(1;11)(q21;q23) in myeloid or lymphoid neoplasm and attempted to summarize these published data. Of interest, pediatric patients displayed a significant larger portion of unique balanced translocations (n = 40), while complex karyotypes were less often identified (n = 12). Vice versa, in adult leukemia patients, complex karyotypes (n = 5) were more frequent than unique balanced translocations (n = 2).