Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia.
MLLT10 (previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms. In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients. We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-year-old male. An inversion of 11q13-q23 with a breakpoint in the MLL gene was followed by an additional break 3' of MLL prior to insertion of the 11q segment into MLLT10. In a second patient, a 37-year-old male with AML-M5b, molecular cytogenetic analysis of an apparent 10;11 reciprocal translocation showed an intrachromosomal inversion of 3'MLLT10followed by a reciprocal translocation between 10p12 and 11q23. Review of the literature showed that all cases were the result of an inversion of either 10p or 11q followed by translocation 10p;11q or insertion of the inverted segment into MLLT10 or MLL.
Van Limbergen
H
H
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Poppe
B
B
Janssens
A
A
De Bock
R
R
De Paepe
A
A
Noens
L
L
Speleman
F
F
D000208:Acute Disease; D000328:Adult; D000368:Aged; D019677:Artificial Gene Fusion; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C092513:MLLT10 protein, human; D014157:Transcription Factors