title: The MLL recombinome of acute leukemias.
abstract: Chromosomal rearrangements of the human MLL gene are a hallmark for aggressive (high-risk) pediatric, adult and therapy-associated acute leukemias. These patients need to be identified in order to subject these patients to appropriate therapy regimen. A recently developed long-distance inverse PCR method was applied to genomic DNA isolated from individual acute leukemia patients in order to identify chromosomal rearrangements of the human MLL gene. We present data of the molecular characterization of 414 samples obtained from 272 pediatric and 142 adult leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified. The combined data of our study and published data revealed a total of 87 different MLL rearrangements of which 51 TPGs are now characterized at the molecular level. Interestingly, the four most frequently found TPGs (AF4, AF9, ENL and AF10) encode nuclear proteins that are part of a protein network involved in histone H3K79 methylation. Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected.
authors.affiliation: Institute of Pharmaceutical Biology/ZAFES/Diagnostic Center of Acute Leukemia, University of Frankfurt, Frankfurt/Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.forename: B
authors.initials: B
authors.lastname: Schneider
authors.forename: S
authors.initials: S
authors.lastname: Jakob
authors.forename: S
authors.initials: S
authors.lastname: Strehl
authors.forename: A
authors.initials: A
authors.lastname: Attarbaschi
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
authors.forename: C
authors.initials: C
authors.lastname: Schoch
authors.forename: M W J C
authors.initials: MW
authors.lastname: Jansen
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: M L
authors.initials: ML
authors.lastname: den Boer
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: M-G
authors.initials: MG
authors.lastname: Ennas
authors.forename: E
authors.initials: E
authors.lastname: Angelucci
authors.forename: U
authors.initials: U
authors.lastname: Koehl
authors.forename: J
authors.initials: J
authors.lastname: Greil
authors.forename: F
authors.initials: F
authors.lastname: Griesinger
authors.forename: U
authors.initials: U
authors.lastname: Zur Stadt
authors.forename: C
authors.initials: C
authors.lastname: Eckert
authors.forename: T
authors.initials: T
authors.lastname: Szczepański
authors.forename: F K
authors.initials: FK
authors.lastname: Niggli
authors.forename: B W
authors.initials: BW
authors.lastname: Schäfer
authors.forename: H
authors.initials: H
authors.lastname: Kempski
authors.forename: H J M
authors.initials: HJ
authors.lastname: Brady
authors.forename: J
authors.initials: J
authors.lastname: Zuna
authors.forename: J
authors.initials: J
authors.lastname: Trka
authors.forename: L L
authors.initials: LL
authors.lastname: Nigro
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: E
authors.initials: E
authors.lastname: Delabesse
authors.forename: E
authors.initials: E
authors.lastname: Macintyre
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: T
authors.initials: T
authors.lastname: Burmeister
authors.forename: T
authors.initials: T
authors.lastname: Dingermann
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: R
authors.initials: R
authors.lastname: Marschalek
mesh_terms: D000208:Acute Disease; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008745:Methylation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D006657:Histones; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase