title: The partial nontandem duplication of the MLL (ALL1) gene is a novel rearrangement that generates three distinct fusion transcripts in B-cell acute lymphoblastic leukemia.
abstract: A partial nontandem duplication (PNTD) of mixed lineage leukemia (MLL) gene is described in B-cell acute lymphoid leukemia without structural cytogenetic abnormalities at 11q23 and 9p22. A duplicated portion of MLL is interrupted by the insertion of a region of 9p22 that includes the 3'-end of the AF9 gene. The PNTD encodes: (a) a PNTD transcript; (b) a partial tandem duplication of MLL; and (c) a chimeric transcript fusing MLL to the 3'-end of AF9, mimicking the t(9;11)(p22;q23) and expressed 1024-fold higher than the other two. The MLL PNTD, therefore, contributes toward leukemogenesis through simultaneous production of fusion transcripts that are otherwise encoded by three distinct genetic defects.
authors.affiliation: Division of Hematology and Oncology, The Ohio State University, Columbus 43210, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Whitman
authors.forename: M P
authors.initials: MP
authors.lastname: Strout
authors.forename: G
authors.initials: G
authors.lastname: Marcucci
authors.forename: A G
authors.initials: AG
authors.lastname: Freud
authors.forename: L L
authors.initials: LL
authors.lastname: Culley
authors.forename: N J
authors.initials: NJ
authors.lastname: Zeleznik-Le
authors.forename: K
authors.initials: K
authors.lastname: Mrózek
authors.forename: K S
authors.initials: KS
authors.lastname: Theil
authors.forename: U R
authors.initials: UR
authors.lastname: Kees
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000235:genetics*; D019457:Chromosome Breakage; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C489901:MLLT3 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase