The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene.
The gene on chromosome 10 at band p12 (AF10), involved in the t(10;11) translocation in acute myeloid leukemia, has been identified and shown to contain conserved zinc finger and leucine zipper domains. These regions are highly homologous to the equivalent regions on AF17, the gene involved in the t(11;17) translocations. A series of adult, childhood, and infant leukemias with either simple or complex versions of the t(10;11) has been examined by Southern analysis and shown to involve rearrangement to the HRX locus. Reverse transcriptase-polymerase chain reaction from either bone marrow or peripheral blood cells showed that HRX sequence was fused to AF10 sequence in all 8 cases and subsequent sequence analysis showed an in-frame fusion between the HRX and AF10 sequence. A consistent feature of these fusions was the juxtaposition of the leucine dimerization motif of AF10 onto the NH2-terminal region of HRX. The published data suggest that a similar conclusion can be drawn about the t(11;17) translocation, implying a critical role for this motif in the chimaeric HRX protein.
Chaplin
T
T
Imperial Cancer Research Fund, Department of Medical Oncology, St Bartholomew's Hospital Medical College, London, UK.
Bernard
O
O
Beverloo
H B
HB
Saha
V
V
Hagemeijer
A
A
Berger
R
R
Young
B D
BD
D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10 / Q000648:ultrastructure*; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005796:Genes; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D016350:Leucine Zippers / Q000235:genetics*; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D012326:RNA Splicing; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C092513:MLLT10 protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase