AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14)

• Published in: Oncogene Vol. 19; no. 38; pp. 4446 - 4450
• Main Authors: HAYETTE, S, TIGAUD, I, VANIER, A, MARTEL, S, CORBO, L, CHARRIN, C, BEILLARD, E, DELEAGE, G, MAGAUD, J. P, RIMOKH, R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 07-09-2000; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Acute myeloid leukemia; AF15q14 gene; Amino Acid Sequence; Amino acids; Artificial Gene Fusion; Base Sequence; Biochemistry, Molecular Biology; Biological and medical sciences; Cell lines; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome 11; Chromosome 15; Chromosomes; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 15; Cloning; Cloning, Molecular; DNA-Binding Proteins; DNA-Binding Proteins - genetics; Expression vectors; Fundamental and applied biological sciences. Psychology; Fusion protein; Gene rearrangement; Genes; Histone-Lysine N-Methyltransferase; Homology; Humans; Immunofluorescence; Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Acute - genetics; Life Sciences; Localization; Male; Middle Aged; MLL gene; MLL protein; Molecular and cellular biology; Molecular Sequence Data; Myeloid-Lymphoid Leukemia Protein; Proteins; Proto-Oncogenes; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Stem cells; Transcription Factors; Transcription, Genetic; Translocation, Genetic; France; Chromosomal aberration; Human; Nucleotide sequence; Acute; Cell nucleus; Malignant hemopathy; Gene expression; Carcinogenesis; Lymphoproliferative syndrome; Abnormal chromosome; Acute lymphocytic leukemia; Localization; Fusion protein; Chromosome translocation
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203789

In haematopoietic malignancies the MLL gene, located on chromosome 11q23, is frequently disrupted by chromosome rearrangement, generally resulting in fusion to various partner genes. We have previously reported a t(11;15)(q23;q14) in a case of acute myeloblastic leukaemia. Here, we report the cloning of a novel MLL partner, AF15q14, at chromosome 15q14. In this translocation, the breakpoint occurred in exon 8 of MLL and exon 10 of AF15q14. The normal AF15q14 transcripts of approximately 8.5 kb in size, are expressed in different tumoral cell lines, in a variety of normal tissues, and in all the foetal tissues tested. Sequencing of AF15q14 cDNA revealed a putative open reading frame of 1833 amino acids that had no homology with any other known protein. The C-terminal end of the putative AF15q14 contained a bipartite nuclear localization site. The translocation t(11;15) preserved the open reading frame between MLL and the 3' end of AF15q14. The contribution of AF15q14 to the fusion protein was only 85 amino acids. Immunofluorescence staining experiments with expression vectors encoding these 85 amino acids confirmed the functionality of the predicted nuclear localization site.