Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineageleukemia protein in a therapy-related leukemia with t(3;11) (p21;q23)

The mixed lineage leukemia (MLL) gene located at chromosome band 11q23 is f requently rearranged in patients with therapy-related acute monocytic leuke mia who received topoisomerase II inhibitors. We have identified a novel fu sion partner of MLL (FAB M5b) in a patient who developed t-AML 9 years afte r treatment for acute lymphoblastic leukemia (ALL), The leukemic cells had a sale karyotypic abnormality of t(3;11) (p21;q23), Screening of a genomic DNA library, prepared from leukemic cell DNA, Identified rearranged crones composed of MLL and a novel gene on chromosome 3p21 (AF3p21). The AF3p21 ge ne encodes a protein of 722 amino acids, which contains an Src homology 3 ( SH3) domain, a proline-rich domain, and a bipartite nuclear localizing sign al (NLS). RNA analysis demonstrated that exon 6 of the MLL gene fused to ex on 2 of the AF3p21 gene, The resulting chimeric protein consists of AT-hook s, methyltransferase, and transcription repressor domains of MLL in additio n to the AF3p21 proline-rich domain and NLS but not the AF3p21 SH3 domain. (C) 2000 by The American Society of Hematology.