PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22).
The AML1 gene (also known as RUNX1) at 21q22 codes for core binding factor (CBF) alpha, which forms a heterodimer with CBF beta that acts as a transcriptional activating factor. CBF is a critical regulator in the generation and differentiation of definitive hematopoietic stem cells and is frequently disrupted in leukemia through chromosome translocations. We cloned a novel AML1 partner gene, PRDX4, in an X;21 translocation in a 74-year-old male patient diagnosed with acute myeloid leukemia-M2. Chromosome analysis detected a t(X;21)(p22;q22) as the sole abnormality in bone marrow samples. The involvement of AML1 was confirmed by fluorescence in situ hybridization studies. Using 3' RACE-PCR, we cloned a fusion between exon 5 of AML1 and exon 2 of PRDX4. RT-PCR confirmed the fusion and detected another fusion between exon 6 of AML1 and exon 2 of PRDX4, indicating alternative splicing of exon 6 of AML1 in the fusion transcripts. PRDX4 is one of six peroxiredoxin-family genes that are highly conserved in eukaryotes and prokaryotes and are ubiquitously expressed. Peroxiredoxin genes exhibit thioredoxin-dependent peroxidase activity and have been implicated in a number of other cellular functions such as cell proliferation and differentiation. PRDX4 plays a regulatory role in the activation of the transcription factor NF-kappaB and is significantly down-regulated in acute promyelocytic leukemia. This is the first example of antioxidant enzyme involvement in a chromosome translocation in leukemia.
Zhang
Yanming
Y
Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637, USA.
Emmanuel
Neelmini
N
Kamboj
Ginny
G
Chen
Jianjun
J
Shurafa
Muhammad
M
Van Dyke
Daniel L
DL
Wiktor
Anne
A
Rowley
Janet D
JD
D000368:Aged; D001483:Base Sequence / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D020732:Cytogenetic Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D007621:Karyotyping / Q000379:methods; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010544:Peroxidases; D054464:Peroxiredoxins; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016364:Reading Frames / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors; D010544:Peroxidases; C515980:PRDX4 protein, human; D054464:Peroxiredoxins