Common gene expression signatures in t(8;21)- and inv(16)-acute myeloid leukaemia.
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).
Ichikawa
Hitoshi
H
Cancer Transcriptome Project, National Cancer Centre Research Institute, Chuo-ku, Tokyo, Japan.
Tanabe
Kenji
K
Mizushima
Hiroshi
H
Hayashi
Yasuhide
Y
Mizutani
Shuki
S
Ishii
Eiichi
E
Hongo
Teruaki
T
Kikuchi
Akira
A
Satake
Masanobu
M
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
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