title: Common gene expression signatures in t(8;21)- and inv(16)-acute myeloid leukaemia.
abstract: Human acute myeloid leukaemia (AML) involving a core-binding factor (CBF) transcription factor is called CBF leukaemia. In these leukaemias, AML1 (RUNX1, PEBP2alphaB, CBFalpha2)-MTG8 (ETO) and CBFbeta (PEBP2beta)-MYH11 chimaeric proteins are generated by t(8;21) and inv(16) respectively. We analysed gene expression profiles of leukaemic cells by microarray, and selected genes whose expression appeared to be modulated in association with t(8;21) and inv(16). In a pair-wise comparison, 15% of t(8;21)-associated transcripts exhibited high or low expression in inv(16)-AML, and 26% of inv(16)-associated transcripts did so equivalently in t(8;21)-AML. These common elements in gene expression profiles between t(8;21)- and inv(16)-AML probably reflect the situation that AML1-MTG8 and CBFbeta-MYH11 chimaeric proteins affect a common set of target genes in CBF leukaemic cells. On the other hand, 38% of t(8;21)-associated and 24% of inv(16)-associated transcripts were regulated in t(8;21)- and inv(16)-specific manners. These distinct features of t(8;21)- and inv(16)-associated genes correlate with the bimodular structures of the chimaeric proteins (CBF-related AML1 and CBFbeta portions, and CBF-unrelated MTG8 and MYH11 portions).
authors.affiliation: Cancer Transcriptome Project, National Cancer Centre Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Teruaki
authors.initials: T
authors.lastname: Hongo
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Satake
mesh_terms: D000208:Acute Disease; D002648:Child; D007446:Chromosome Inversion / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D016000:Cluster Analysis; D050660:Core Binding Factors / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
chemical_list: C095514:CBFbeta-MYH11 fusion protein; D050660:Core Binding Factors; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D014157:Transcription Factors