ABI-1, A HUMAN HOMOLOG TO MOUSE ABL-INTERACTOR-1, FUSES THE MLL GENE IN ACUTE MYELOID-LEUKEMIA WITH T(10-11)(P11.2-Q23)

Recurrent translocation t(10;11) has been reported to be associated wi th acute myeloid leukemia (AML). Recently, two types of chimeric trans cripts, MLL-AF10 in t(10;11)(p12; q23) and CALM-AF10 in t(10;11)(p13;q 14), were isolated. t(10;11) is strongly associated with complex trans locations, including invins (10:11) and inv(11)t(10:11), because the d irection of transcription of AFIO is telomere to centromere. We analyz ed a patient of AML with t(10;11)(p11.2;q23) and identified ABI-I on c hromosome 10p11.2, a human homolog to mouse Abl-interactor 1 (Abi-1), fused with MLL. Whereas the ABI-1 gene bears no homology with the part ner genes of MLL previously described, the ABI-1 protein exhibits sequ ence similarity to protein of homeotic genes, contains several polypro line stretches, and includes a src homology 3 (SH3) domain at the C-te rminus that is required for binding to Abl proteins in mouse Abi-l pro tein. Recently, e3B1, an eps8 SH3 binding protein 1, was also isolated as a human homolog to mouse Abi-l. Three types of transcripts of ABI- 1 gene were expressed in normal peripheral blood. Although e3B1 was co nsidered to be a full-length ABI-1, the MLL-ABI-1 fusion transcript in this patient was formed by an alternatively spliced ABI-1. Others hav e shown that mouse Abi-l suppresses v-ABL transforming activity and th at e3B1, full-length ABI-1, regulates cell growth. In-frame MLL-ABI-1 fusion transcripts combine the MLL AT-hook motifs and DNA methyltransf erase homology region with the homeodomain homologous region, polyprol ine stretches, and SH3 domain of alternatively spliced transcript of A BI-1. Our results suggest that the ABI-1 gene plays a role in leukemog enesis by translocating to MLL, (C) 1998 by The American Society of He matology.