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The HOXD11 Gene Is Fused to the NUP98 Gene in Acute Myeloid Leukemia with t(2;11)(q31;p15)¹

Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan [T. Take., T. Taki, N. S., Y. H.]; Department of Pediatrics, Shimane Medical University, Shimane 693-8501, Japan [T. Take.]; and Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Aomori 036-8562, Japan [E. I., J. K., K. T.]

The nucleoporin gene, NUP98, has been reported to be fused to seven partner genes in hematological malignancies with 11p15 translocations. We report here a novel NUP98 partner gene, HOXD11, not HOXD13, in a pediatric patient with de novo AML having t(2;11)(q31;p15), using a cDNA panhandle PCR. The HOXD11 gene is one of the HOXD cluster genes and contains 2 exons, encoding a protein of 338 amino acids with a homeodomain. Reverse transcription (RT)-PCR analysis showed that two alternatively spliced 5'-NUP98 transcripts were fused in frame to the HOXD11 gene. Both proteins consist of an NH₂-terminal phenylalanine-glycine repeat motif of NUP98 and COOH-terminal homeodomain of HOXD11. RT-PCR analysis in various leukemic cell lines showed that expression of the HOXD11 gene was significantly more frequent in BCR-ABL-positive than in BCR-ABL-negative leukemic cell lines (P = 0.028). Our results revealed that t(2;11)(q31;p15) was not a single chromosomal abnormality and that the NUP98-HOXD fusion genes encode similar fusion proteins, which suggests that the NUP98-HOXD11 as well as NUP98-HOXD13 fusion protein play a role in leukemogenesis through similar mechanisms.

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