title: t(10;11)-acute leukemias with MLL-AF10 and MLL-ABI1 chimeric transcripts: specific expression patterns of ABI1 gene in leukemia and solid tumor cell lines.
abstract: The recurrent translocation t(10;11) is associated with acute myeloid leukemia (AML). The AF10 gene on chromosome 10 at band p12 and MLL at 11q23 fuse in the t(10;11)(p12;q23). Recently, we have identified ABI1 as a new partner gene for MLL in an AML patient with a t(10;11)(p11.2;q23). The ABI1 is a human homologue of the mouse Abl-interactor 1 (Abi1), encoding an Abl-binding protein. The ABI1 protein exhibits sequence similarity to homeotic genes, and contains several polyproline stretches and a src homology 3 (SH3) domain. To clarify the clinical features of t(10;11)-leukemias, we investigated 6 samples from acute leukemia patients with t(10;11) and MLL rearrangement and detected MLL-AF10 chimeric transcripts in 5 samples and MLL-ABI1 in one. The patient with MLL-ABI1 chimeric transcript is the second case described, thus confirming that the fusion of the MLL and ABI1 genes is a recurring abnormality. Both of the patients with MLL-ABI1 chimeric transcript are surviving, suggesting that these patients have a better prognosis than the patients with MLL-AF10. To investigate the roles of AF10 and ABI1 further, we examined the expression of these genes in various cell lines and fresh tumor samples using the reverse transcriptase-polymerase chain reaction method. Although AF10 was expressed in almost all cell lines similarly, the expression patterns of ABI1 were different between leukemia and solid tumor cell lines, suggesting the distinctive role of each isoform of ABI1 in these cell lines. We also determined the complete mouse Abi1 sequence and found that the sequence matched with human ABI1 better than the originally reported Abi1 sequence. Further functional analysis of the MLL-AF10 and MLL-ABI1 fusion proteins will provide new insights into the leukemogenesis of t(10;11)-AML.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shibuya
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.forename: H
authors.initials: H
authors.lastname: Mugishima
authors.forename: M
authors.initials: M
authors.lastname: Chin
authors.forename: M
authors.initials: M
authors.lastname: Tsuchida
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: K
authors.initials: K
authors.lastname: Kawa
authors.forename: E
authors.initials: E
authors.lastname: Ishii
authors.forename: I
authors.initials: I
authors.lastname: Miura
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D029681:Arabidopsis Proteins; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C114045:MLL-ABI1 fusion protein, human; C092513:MLLT10 protein, human; C490477:Mllt10 protein, mouse; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; C087434:ABI1 protein, Arabidopsis; D010749:Phosphoprotein Phosphatases