title: A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15.
abstract: The mixed lineage leukemia gene (MLL, also known as HRX, ALL-1 and Htrx) located at 11q23 is involved in translocations with over 40 different chromosomal bands in a variety of leukemia subtypes. Here we report our analysis of a rare but recurring translocation, t(11;15)(q23;q14). This translocation has been described in a small subset of cases with both acute myeloblastic leukemia and ALL. Recent studies have shown that MLL is fused to AF15q14 in the t(11;15). Here we analyse a sample from another patient with this translocation and confirm the presence of an MLL-AF15q14 fusion. However, we have also identified and cloned another fusion transcript from the same patient sample. In this fusion transcript, MLL is fused to a novel gene, MLL partner containing FYVE domain (MPFYVE). Both MLL-AF15q14 and MLL-MPFYVE are in-frame fusion transcripts with the potential to code for novel fusion proteins. MPFYVE is also located on chromosome 15, approximately 170 kb telomeric to AF15q14. MPFYVE contains a highly conserved motif, the FYVE domain which, in other proteins, has been shown to bind to phosphotidyl-inositol-3 phosphate (PtdIns(3)P). The MLL-MPFYVE fusion may be functionally important in the leukemia process in at least some patients containing this translocation.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, IL 60637, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Chinwalla
authors.forename: Andy
authors.initials: A
authors.lastname: Chien
authors.forename: Maria
authors.initials: M
authors.lastname: Odero
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Neilly
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Zeleznik-Le
authors.forename: Janet D
authors.initials: JD
authors.lastname: Rowley
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics* / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000502:physiology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; C472641:MLL-AF15q14 fusion protein, human; C472642:MLL-MPFYVE fusion protein, human; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; C472640:ZFYVE19 protein, human; D051788:Myeloid-Lymphoid Leukemia Protein