The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15)

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 1; pp. 33 - 37
• Main Authors: TAKETANI, Takeshi, TAKI, Tomohiko, SHIBUYA, Noriko, ITO, Etsuro, KITAZAWA, Junichi, TERUI, Kiminori, HAYASHI, Yasuhide
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 2002
• Subjects: ABL gene; Adolescent; Amino Acid Sequence; Artificial Gene Fusion; Base Sequence; BCR gene; Biological and medical sciences; Blotting, Southern; chromosome 11; chromosome 2; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 2; DNA, Neoplasm - genetics; Gene Expression Regulation, Leukemic; Hematologic and hematopoietic diseases; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; HOXD11 gene; HOXD13 gene; Humans; Leukemia, Myelomonocytic, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Molecular Sequence Data; Nuclear Pore Complex Proteins - biosynthesis; Nuclear Pore Complex Proteins - genetics; nucleoporins; NUP98 gene; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Transcription Factors - biosynthesis; Transcription Factors - genetics; Translocation, Genetic - genetics; Chromosomal aberration; Human; Acute; Hematopoietic cell; Chromosome A2; Malignant hemopathy; Gene expression; Chromosome C11; In vitro; Case study; Bone marrow; Abnormal chromosome; Molecular domain; Hybrid gene; Acute myelocytic leukemia; Chromosome translocation
• ISSN: 0008-5472; 1538-7445

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.