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New insights to the MLL recombinome of acute leukemias

Lookup NU author(s): Professor Olaf Heidenreich

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Abstract

Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.

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Author(s): Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J, Abdelali RB, Macintyre E, De Braekeleer E, De Braekeleer M, Delabesse E, De Oliveira MP, Cave H, Clappier E, van Dongen JJ, Balgobind BV, van den Heuvel-Eibrink MM, Beverloo HB, Panzer-Grumayer R, Teigler-Schlegel A, Harbott J, Kjeldsen E, Schnittger S, Koehl U, Gruhn B, Heidenreich O, Chan LC, Yip SF, Krzywinski M, Eckert C, Moricke A, Schrappe M, Alonso CN, Schafer BW, Krauter J, Lee DA, Zur Stadt U, Te Kronnie G, Sutton R, Izraeli S, Trakhtenbrot L, Lo Nigro L, Tsaur G, Fechina L, Szczepanski T, Strehl S, Ilencikova D, Molkentin M, Burmeister T, Dingermann T, Klingebiel T, Marschalek R

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2009

Volume: 23

Issue: 8

Pages: 1490-1499

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/leu.2009.33

DOI: 10.1038/leu.2009.33

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