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The MLL recombinome of acute leukemias in 2017

Lookup NU author(s): Professor Olaf Heidenreich, Professor Josef Vormoor

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© The Author(s) 2018.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.


Publication metadata

Author(s): Meyer C, Burmeister T, Groger D, Tsaur G, Fechina L, Renneville A, Sutton R, Venn NC, Emerenciano M, Pombo-De-Oliveira MS, Barbieri Blunck C, Almeida Lopes B, Zuna J, Trka J, Ballerini P, Lapillonne H, De Braekeleer M, Cazzaniga G, Corral Abascal L, Van Der Velden VHJ, Delabesse E, Park TS, Oh SH, Silva MLM, Lund-Aho T, Juvonen V, Moore AS, Heidenreich O, Vormoor J, Zerkalenkova E, Olshanskaya Y, Bueno C, Menendez P, Teigler-Schlegel A, Zur Stadt U, Lentes J, Gohring G, Kustanovich A, Aleinikova O, Schafer BW, Kubetzko S, Madsen HO, Gruhn B, Duarte X, Gameiro P, Lippert E, Bidet A, Cayuela JM, Clappier E, Alonso CN, Zwaan CM, Van Den Heuvel-Eibrink MM, Izraeli S, Trakhtenbrot L, Archer P, Hancock J, Moricke A, Alten J, Schrappe M, Stanulla M, Strehl S, Attarbaschi A, Dworzak M, Haas OA, Panzer-Grumayer R, Sedek L, Szczepa T, Caye A, Suarez L, Cave H, Marschalek R

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2018

Volume: 32

Issue: 2

Pages: 273-284

Online publication date: 13/07/2017

Acceptance date: 21/06/2017

Date deposited: 08/03/2018

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/leu.2017.213

DOI: 10.1038/leu.2017.213


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