Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints.
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.
Atlas
M
M
Department of Pediatrics, Northwestern University, Chicago, IL, USA.
Head
D
D
Behm
F
F
Schmidt
E
E
Zeleznik-Le
N H
NH
Roe
B A
BA
Burian
D
D
Domer
P H
PH
D000208:Acute Disease; D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011519:Proto-Oncogenes; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase