Herein we present a novel case of acute undifferentiated leukemia with SET-NUP214 rearrangement due to the cryptic deletion of the 9q34 region producing two different types of fusion transcripts by alternative splicing and molecular characterization of the fusion transcripts by fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction, and array comparative genomic hybridization analyses.
SET-CAN associated with the t(9;9) in acute undifferentiated leukemia encodes almost the entire sequence of SET and the C-terminal two-third portion of CAN, including the FG repeat region.
SETBP1 has previously not been implicated in leukaemias; however, it encodes a protein that specifically interacts with SET, fused to NUP214 in a case of acute undifferentiated leukaemia.
This suggests that SET-CAN expression in acute undifferentiated leukemia might determine the primitive phenotype of the disease, whereas secondary genetic lesions are necessary for disease development.
Nucleotide sequence analysis revealed that the 39-kDa polypeptide corresponds to the protein encoded by the set gene, which is the part of the putative oncogene associated with acute undifferentiated leukemia when translocated to the can gene.
SET is fused to a putative oncoprotein, CAN, in AUL and is thought to regulate the transformation potential of SET-CAN by its nuclear localization and phosphorylation.
Although the function(s) of SET and SET-CAN is not known, we propose that SET plays a key role in the mechanism of leukemogenesis in acute undifferentiated leukemia, perhaps by activating CAN in nuclei and stimulating the transformation potential of SET-CAN.