Journal Article

The MLL recombinome of acute leukemias in 2013

Gröger, D, Villarese, P, De Braekeleer, E, Hancock, J, Park, T S, Sedék, L, Vormoor, J, Wehner, S, Silva, M L M, Henry, C, Callanan, M B, Klingebiel, T, Pombo de Oliveira, M, Burmeister, T, Harris, M H, Jarosova, M, Ballerini, P, Kolenova, A, Lee, D S, Marschalek, R, Choi, J R, Kakadiya, P M, Fechina, L, Delabesse, E, Menendez, P, Zuna, J, Cazzaniga, G, Bohlander, S, Aleinikova, O, Szczepański, T, Lapillone, H, van der Velden, V H J, Eckert, C, Renneville, A, Cerveira, N, Coenen, E A, Meyer, C, van den Heuvel-Eibrink, M M, Heidenreich, O, Izraeli, S, Cavé, H, Archer, P, Talmant, P, Choi, W W L, Dworzak, M, zur Stadt, U, Bueno, C, Clappier, E, Panzer-Grümayer, R, Trka, J, van Dongen, J J M, Tsaur, G, Emerenciano, M, Madsen, H O, Mass-Malo, K, Lippert, E, Macintyre, E, Juvonen, V, Hofmann, J, Tondeur, S, Schäfer, B W, Cayuela, J M, Ahlmann, M, Binato, R, Gameiro, P, Möricke, A, Stanulla, M, Strehl, S, Lund-Aho, T, Herbaux, C, Schrappe, M, Kustanovich, A, Teixeira, M R, Zwaan, C M, Oh, S H, Krauter, J, Dingermann, T, Cornillet-Lefebvre, P, Sutton, R, Trakhtenbrot, L, Launay, E, De Braekeleer, M, Kubetzko, S, Alonso, C N, Venn, N C, Te Kronnie, G, Lo Nigro,

2013

Overview

Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL -rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4 , MLLT3/AF9 , MLLT1/ENL , MLLT10/AF10 , ELL , partial tandem duplications ( MLL PTDs) and MLLT4/AF6 , respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Springer Nature
• Subject: 692/699/67/1990/283 / 692/699/67/69 / Acute Disease / Adolescent / Adult / AF4 protein / Age Factors / Aged / Aged, 80 and over / Animals / Antibody diversity / Biochemistry / Biology / Cancer / Cancer Research / Child / Child, Preschool / Chromosome Breakage / Chromosome mapping / Critical Care Medicine / Female / Gene Rearrangement / Genetic aspects / Hematology / Histone-Lysine N-Methyltransferase / Humans / Immunology / Infant / Infant, Newborn / Intensive / Internal Medicine / Laboratories / Leukemia / Leukemia - classification / Leukemia - genetics / Life Sciences / Male / Medical research / Medicine / Medicine & Public Health / Methods / Mice / Middle Aged / Myeloid-Lymphoid Leukemia Protein / Myeloid-Lymphoid Leukemia Protein - genetics / Oncogene Proteins, Fusion / Oncogene Proteins, Fusion - genetics / Oncology / Original / original-article / Pathology / Pediatrics / Pharmacy / Polymerase Chain Reaction / Prognosis / Research centers / Testing / Translocation, Genetic / Translocation, Genetic - genetics / University colleges / Young Adult