title: The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15).
abstract: 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 NH(2)-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.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Noriko
authors.initials: N
authors.lastname: Shibuya
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitazawa
authors.forename: Kiminori
authors.initials: K
authors.lastname: Terui
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D019677:Artificial Gene Fusion; D001483:Base Sequence; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11; D002889:Chromosomes, Human, Pair 2; D004273:DNA, Neoplasm / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C489493:HOXD11 protein, human; D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C093350:nuclear pore complex protein 98