Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2.
Chromosomal abnormalities in acute leukemia have led to the discovery of many genes involved in normal hematopoiesis and in malignant transformation. We have identified the fusion partners in an inv(8)(p11q13) from a patient with acute mixed lineage leukemia. We show by fluorescence in situ hybridization (FISH) analysis, Southern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) that the genes for MOZ, monocytic leukemia zinc finger protein, and TIF2, transcriptional intermediary factor 2, are involved in the inv(8)(p11q13). We demonstrate that the inversion creates a fusion between the 5' end of MOZ mRNA and the 3' end of TIF2 mRNA maintaining the translational frame of the protein. The predicted fusion protein contains the zinc finger domains, the nuclear localization domains, the histone acetyltransferase (HAT) domain, and a portion of the acidic domain of MOZ, coupled to the CREB-binding protein (CBP) interaction domain and the activation domains of TIF2. The breakpoint is distinct from the breakpoint in the t(8;16)(p11;p13) translocation in acute monocytic leukemia with erythrophagocytosis that fuses MOZ with CBP. The reciprocal TIF2-MOZ fusion gene is not expressed, perhaps as a result of a deletion near the chromosome 8 centromere. The MOZ-TIF2 fusion is one of a new family of chromosomal rearrangements that associate HAT activity, transcriptional coactivation, and acute leukemia.
Liang
J
J
Department of Molecular Biology and Biochemistry, Pediatrics, Urology, and Medicine, the Feist-Weiller Cancer Center, Louisiana State University Medical School, Shreveport, LA, USA.
Prouty
L
L
Williams
B J
BJ
Dayton
M A
MA
Blanchard
K L
KL
D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D015139:Blotting, Southern; D002869:Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics*; D025063:Chromosome Disorders; D007446:Chromosome Inversion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015456:Leukemia, Biphenotypic, Acute / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D051958:Nuclear Receptor Coactivator 2; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014178:Translocation, Genetic
C498001:NCOA2 protein, human; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human; D012194:RNA-Directed DNA Polymerase