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The MLL recombinome of acute leukemias in 2017.

  • Meyer C Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University, Frankfurt/Main, Germany.
  • Burmeister T Charité-Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany.
  • Gröger D Charité-Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany.
  • Tsaur G Regional Children Hospital 1, Research Institute of Medical Cell Technologies, Pediatric Oncology and Hematology Center, Ural Federal University, Ekaterinburg, Russia.
  • Fechina L Regional Children Hospital 1, Research Institute of Medical Cell Technologies, Pediatric Oncology and Hematology Center, Ural Federal University, Ekaterinburg, Russia.
  • Renneville A Laboratory of Hematology, Biology and Pathology Center, CHRU of Lille; INSERM, UMR-S 1172, Cancer Research Institute of Lille, Lille, France.
  • Sutton R Children's Cancer Institute Australia, Uinversity of NSW Sydney, Sydney, New South Wales, Australia.
  • Venn NC Children's Cancer Institute Australia, Uinversity of NSW Sydney, Sydney, New South Wales, Australia.
  • Emerenciano M Pediatric Hematology-Oncology Program-Research Center, Instituto Nacional de Cancer Rio de Janeiro, Rio de Janeiro, Brazil.
  • Pombo-de-Oliveira MS Pediatric Hematology-Oncology Program-Research Center, Instituto Nacional de Cancer Rio de Janeiro, Rio de Janeiro, Brazil.
  • Barbieri Blunck C Pediatric Hematology-Oncology Program-Research Center, Instituto Nacional de Cancer Rio de Janeiro, Rio de Janeiro, Brazil.
  • Almeida Lopes B Pediatric Hematology-Oncology Program-Research Center, Instituto Nacional de Cancer Rio de Janeiro, Rio de Janeiro, Brazil.
  • Zuna J CLIP, Department of Paediatric Haematology/Oncology, Charles University Prague, 2nd Faculty of Medicine, Prague, Czech Republic.
  • Trka J CLIP, Department of Paediatric Haematology/Oncology, Charles University Prague, 2nd Faculty of Medicine, Prague, Czech Republic.
  • Ballerini P Biological Hematology, AP-HP A. Trousseau, Pierre et Marie Curie University, Paris, France.
  • Lapillonne H Biological Hematology, AP-HP A. Trousseau, Pierre et Marie Curie University, Paris, France.
  • De Braekeleer M Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, Laboratoire d'Histologie, Embryologie et Cytogénétique & INSERM-U1078, Brest, France.
  • Cazzaniga G Centro Ricerca Tettamanti, Clinica Pediatrica Univ. Milano Bicocca, Monza, Italy.
  • Corral Abascal L Centro Ricerca Tettamanti, Clinica Pediatrica Univ. Milano Bicocca, Monza, Italy.
  • van der Velden VHJ Erasmus MC, Department of Immunology, Rotterdam, The Netherlands.
  • Delabesse E CHU Purpan, Laboratoire d'Hématologie, Toulouse, France.
  • Park TS Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
  • Oh SH Department of Laboratory Medicine, Inje University College of Medicine, Busan, Korea.
  • Silva MLM Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, Brazil.
  • Lund-Aho T Laboratory of Clinical Genetics, Fimlab Laboratories, Tampere, Finland.
  • Juvonen V Department of Clinical Chemistry and TYKSLAB, University of Turku and Turku University Central Hospital, Turku, Finland.
  • Moore AS The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • Heidenreich O Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
  • Vormoor J The Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Zerkalenkova E Dmitry Rogachev National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, Moscow.
  • Olshanskaya Y Dmitry Rogachev National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology, Moscow.
  • Bueno C Josep Carreras Leukemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain.
  • Menendez P Josep Carreras Leukemia Research Institute, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain.
  • Teigler-Schlegel A Department of Experimental Pathology and Cytology, Institute of Pathology, Giessen, Germany.
  • Zur Stadt U Center for Diagnostic, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
  • Lentes J Department of Human Genetics, Hannover Medical School, Hanover, Germany.
  • Göhring G Department of Human Genetics, Hannover Medical School, Hanover, Germany.
  • Kustanovich A Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus.
  • Aleinikova O Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus.
  • Schäfer BW Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
  • Kubetzko S Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
  • Madsen HO Department of Clinical Immunology, University Hospital Rigshospitalet, Copenhagen, Denmark.
  • Gruhn B Department of Pediatrics, Jena University Hospital, Jena, Germany.
  • Duarte X Department of Pediatrics, Portuguese Institute of Oncology of Lisbon, Lisbon, Portugal.
  • Gameiro P Hemato-Oncology Laboratory, UIPM, Portuguese Institute of Oncology of Lisbon, Lisbon, Portugal.
  • Lippert E Hématologie Biologique, CHU de Brest and INSERM U1078, Université de Bretagne Occidentale, Brest, France.
  • Bidet A Hématologie Biologique, CHU de Brest and INSERM U1078, Université de Bretagne Occidentale, Brest, France.
  • Cayuela JM Laboratoire d'hématologie, AP-HP Saint-Louis, Paris Diderot University, Paris, France.
  • Clappier E Laboratoire d'hématologie, AP-HP Saint-Louis, Paris Diderot University, Paris, France.
  • Alonso CN Hospital Nacional de Pediatría Prof Dr J. P. Garrahan, Servcio de Hemato-Oncología, Buenos Aires, Argentina.
  • Zwaan CM Department of Pediatric Oncology/Hematology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands.
  • van den Heuvel-Eibrink MM Department of Pediatric Oncology/Hematology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands.
  • Izraeli S The Chaim Sheba Medical Center, Department of Pediatric Hemato-Oncology and the Cancer Research Center, Tel Aviv, Israel.
  • Trakhtenbrot L The Chaim Sheba Medical Center, Department of Pediatric Hemato-Oncology and the Cancer Research Center, Tel Aviv, Israel.
  • Archer P Bristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
  • Hancock J Bristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
  • Möricke A Department of Pediatrics, University Medical Centre Schleswig-Holstein, Kiel, Germany.
  • Alten J Department of Pediatrics, University Medical Centre Schleswig-Holstein, Kiel, Germany.
  • Schrappe M Department of Pediatrics, University Medical Centre Schleswig-Holstein, Kiel, Germany.
  • Stanulla M Department of Pediatrics, MHH, Hanover, Germany.
  • Strehl S Children's Cancer Research Institute and St Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
  • Attarbaschi A Children's Cancer Research Institute and St Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
  • Dworzak M Children's Cancer Research Institute and St Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
  • Haas OA Children's Cancer Research Institute and St Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
  • Panzer-Grümayer R Children's Cancer Research Institute and St Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
  • Sedék L Department of Microbiology and Immunology, Medical University of Silesia, Zabrze, Poland.
  • Szczepański T Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland.
  • Caye A Department of Genetics, AP-HP Robert Debré, Paris Diderot University, Paris, France.
  • Suarez L Department of Genetics, AP-HP Robert Debré, Paris Diderot University, Paris, France.
  • Cavé H Department of Genetics, AP-HP Robert Debré, Paris Diderot University, Paris, France.
  • Marschalek R Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University, Frankfurt/Main, Germany.
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  • 2017-07-14
Published in:
  • Leukemia. - 2018
Adult
Child
Chromosome Aberrations
Chromosome Breakage
Female
Gene Rearrangement
Histone-Lysine N-Methyltransferase
Humans
Infant
Leukemia, Myeloid, Acute
Male
Myeloid-Lymphoid Leukemia Protein
Oncogene Proteins, Fusion
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Translocation, Genetic
English Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/30324
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