Identification of a Novel 11;17 Translocation Involving the NUP98 Gene in Acute Myeloid Leukemia
Chromosomal abnormalities on 17p are associated with a variety of leukemias. We recently identified a patient with acute myeloid leukemia (AML) that presented with a possible chromosomal abnormality on 17p by standard cytogenetic analysis. To confirm involvement of 17p we performed fluorescence in situ hybridization (FISH) with a p53 probe, but a normal signal pattern was observed. Further FISH analysis with a LIS1 probe distal to p53 revealed a subtle balanced 11;17 translocation. We attempted to identify the translocation breakpoints. Considering the NUP98 gene located at 11p15 is commonly involved in translocations resulting in AML, we constructed a breakapart probe set using bacteria artificial chromosome (BAC) clones containing the telomeric and centromeric ends of NUP98. With this probe we demonstrated involvement of NUP98 in the translocation. The breakpoint on chromosome 17 occurred in the region between p53 and LIS1. After constructing and testing a series of BAC clone probes between the two genes we narrowed down the breakpoint to a region containing two closely linked genes, eukaryotic translation initiation factor 5A (eIF5A) and G protein pathway suppressor 2 (GPS2). eIF5A can act as a regulator of p53 and p53-dependent apoptosis, and GPS2 acts in signal repression in G protein-mitogen-activated protein kinase signaling. NUP98 is one of the most promiscuous fusion partner genes in hematological malignancies with more than 20 different fusion partners on various chromosomes; however, the 11;17 translocation in AML is a novel finding. The FISH probes developed in this study have not only provided accurate cytogenetic diagnosis since subtle translocations are difficult to detect but also made it possible to monitor therapy and disease progression. Additionally the NUP98 probe set will be useful to detect other subtle translocations involving this gene.