Abstract
The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify the role topoisomerase II inhibition may play in that mechanism we have cloned and sequenced the breakpoints from four tAML patients with the t(9;11). This sequence analysis identifies topoisomerase II consensus binding sequences near or at the chromosome 11 and chromosome 9 breakpoints in all four patients. One patient also had the consensus binding sequence for the TRANSLIN DNA-binding protein at the 9p22 and 11q23 breakpoints. Our results further support a direct role for topoisomerase II in the genesis of these tAML translocations.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Adolescent
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Amino Acid Sequence
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Base Sequence
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Child
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Child, Preschool
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Chromosomes, Human, Pair 11 / genetics*
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Chromosomes, Human, Pair 9 / genetics*
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Cloning, Molecular
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics*
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Female
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Histone-Lysine N-Methyltransferase
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Humans
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Leukemia, Myeloid / chemically induced
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Leukemia, Myeloid / genetics*
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Male
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Molecular Sequence Data
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Myeloid-Lymphoid Leukemia Protein
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Neoplasm Proteins / analysis
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Neoplasm Proteins / genetics*
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Neoplasms, Second Primary / chemically induced
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Neoplasms, Second Primary / genetics*
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Oncogene Proteins, Fusion / analysis
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Oncogene Proteins, Fusion / genetics*
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Polymerase Chain Reaction / methods
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Proto-Oncogenes*
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Sensitivity and Specificity
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Sequence Analysis, DNA
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Topoisomerase II Inhibitors*
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Transcription Factors*
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Translocation, Genetic*
Substances
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DNA-Binding Proteins
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KMT2A protein, human
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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Topoisomerase II Inhibitors
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Transcription Factors
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Myeloid-Lymphoid Leukemia Protein
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Histone-Lysine N-Methyltransferase