Potential topoisomerase II DNA-binding sites at the breakpoints of a t(9;11) chromosome translocation in acute myeloid leukemia.
We have examined a t(9;11)(p22;q23) chromosome translocation in an acute myeloid leukemia of an infant. The breakpoints on the two chromosomes occurred within introns of the involved genes: AF-9 on chromosome 9, and ALL-1 on chromosome 11. Sequence analysis identified heptamers flanking the breakpoints on both chromosomes 9 and 11, suggesting that the V-D-J recombinase was involved in the translocation. The presence of an N-region between the two chromosomes supports the hypothesis that a mistake in V-D-J joining was involved in the genesis of the translocation and indicates that terminal deoxynucleotidyl transferase was expressed in the cells from which this acute myeloid leukemia originated. In addition, potential topoisomerase II DNA-binding sites were found near the breakpoints of both chromosomes, suggesting the involvement of altered topoisomerase II activity in this translocation. Altered topoisomerase II activity in the presence of an active V-D-J recombinase may be a pathogenetic mechanism of acute myeloid leukemia with rearrangements at 11q23.
Negrini
M
M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Felix
C A
CA
Martin
C
C
Lange
B J
BJ
Nakamura
T
T
Canaani
E
E
Croce
C M
CM
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11; D002899:Chromosomes, Human, Pair 9; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D006801:Humans; D007438:Introns; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D045567:VDJ Recombinases
D004273:DNA, Neoplasm; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases; D004250:DNA Topoisomerases, Type II