Cytogenetics, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction are necessary to clarify the various mechanisms leading to an MLL-AF10 fusion in acute myelocytic leukemia with 10;11 rearrangement.
In acute myelocytic leukemia (AML), predominantly in AML M5a, a recurrent chromosome aberration involves 11q23/MLL and the short arm of chromosome 10. Molecular studies have shown that the AF10 gene at 10p12 is consistently a partner gene in cases with 10;11 rearrangement. A simple reciprocal translocation cannot lead to the known MLL-AF10 fusion transcript because the 3' part of the MLL gene is orientated to the telomere and the 3' part of the AF10 gene to the centromere. In a series of 1897 AML samples, 14 cases (0.74%) showed 10;11 rearrangements leading to a MLL-AF10 fusion transcript. These cases were analyzed in detail with G banding analyses, fluorescence in situ hybridization, and molecular investigation in a single center. Five different mechanisms of (10;11) rearrangements leading to a MLL-AF10 fusion transcript can be observed (i.e., reciprocal translocations, insertions of either 10p into 11q or 11q into 10p, as well as complex and cryptic rearrangements). Compared to translocations involving MLL and other partner genes, complex rearrangements are unique for MLL-AF10 fusions. This may result from the opposite orientation of MLL and AF10.
Klaus
Mirjam
M
Department of Internal Medicine III, Laboratory for Leukemia Diagnostics, Ludwig-Maximilians-University, 81377 Munich, Germany. mirjan.Klaus@med3.med.uni-muenchen.de
Schnittger
Susanne
S
Haferlach
Torsten
T
Dreyling
Martin
M
Hiddemann
Wolfgang
W
Schoch
Claudia
C
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
C470550:MLL-AF10 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein