title: C/EBPbeta suppression by interruption of CUGBP1 resulting from a complex rearrangement of MLL.
abstract: Translocations involving the mixed-lineage leukemia gene (MLL) confer a poor prognosis in acute leukemias. In t(1;11)(q21;q23), MLL is fused reciprocally with AF1q. Here we describe a t(1;11)(q21;q23) with a secondary event involving insertion of the telomeric portion of MLL into the p arm of chromosome 11 (11p11). We show that this latter event interrupts the CUG triplet repeat binding protein-1 (CUGBP1) gene, a translational enhancer of C/EBPbeta. We then showed that these cells have reduced expression of CUGBP1 and C/EBPbeta when compared to other AML blasts. This is the first report to describe insertional disruption of the CUGBP1 gene and to suggest a role for the CUGBP1-C/EBPbeta pathway in leukemogenesis.
authors.affiliation: Division of Pediatrics, Cell Therapy Section, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Pediatrics Research Unit #853, Houston, TX 77030-4009, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Choi
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Folsom
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Azim
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Eric
authors.initials: E
authors.lastname: Kowarz
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Timchenko
authors.forename: Rizwan C
authors.initials: RC
authors.lastname: Naeem
authors.forename: Dean A
authors.initials: DA
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D001483:Base Sequence; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000067879:CELF1 Protein; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D016335:Zinc Fingers
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D000067879:CELF1 Protein; C102843:CELF1 protein, human; C497422:KMT2A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase