The MLL recombinome of acute leukemias

被引：156
|
作者：
Meyer, C
Schneider, B
Jakob, S
Strehl, S
Attarbaschi, A
Schnittger, S
Schoch, C
Jansen, MWJC
Dongen, JJM
Boer, ML
Pieters, R
Ennas, MG
Angelucci, E
Koehl, U
Greil, J
Griesinger, F
zur Stadt, U
Eckert, C
Szczepanski, T
Niggli, FK
Schäfer, BW
Kempski, H
Brady, HJM
Zuna, J
Trka, J
Nigro, LL
Biondi, A
Delabesse, E
Macintyre, E
Stanulla, M
Schrappe, M
Haas, OA
Burmeister, T
Dingermann, T
Klingebiel, T
Marschalek, R
机构：
[1] Univ Frankfurt, Inst Pharmaceut Biol, ZAFES, Diagnost Ctr Acute Leukemia, D-6000 Frankfurt, Germany
[2] CCRI, Vienna, Austria
[3] Univ Munich, Univ Hosp Grosshadern, Dept Internal Med 3, Lab Leukemia Diagnost, Munich, Germany
[4] Erasmus MC, Dept Immunol, Rotterdam, Netherlands
[5] Erasmus MC, Sophia Childrens Hosp, Dept Paediat Oncol Hematol, Rotterdam, Netherlands
[6] Univ Cagliari, Dept Cytomorphol, Cagliari, Italy
[7] Hosp A Businco, Cagliari, Italy
[8] Univ Childrens Hosp, Dept Pediat Hematol & Oncol, Tubingen, Germany
[9] Dept Hematol & Oncol, Gottingen, Germany
[10] Dept Pediat Hematol & Oncol, Hamburg, Germany
[11] Charite Univ Med Berlin, Dept Pediat Oncol & Hematol, Berlin, Germany
[12] Silesian Acad Med, Dept Pediat Hematol & Oncol, Zabrze, Poland
[13] Univ Childrens Hosp, Dept Oncol, Zurich, Switzerland
[14] UCL, Inst Child Hlth, Mol Haematol & Canc Biol Unit, London, England
[15] Charles Univ Prague, Dept Paediat Haematol Oncol, Prague, Czech Republic
[16] Univ Catania, Ctr Pediat Hematol Oncol, Catania, Italy
[17] Univ Milano Bicocca, M Tettamanti Res Ctr, Monza, Italy
[18] AP HP, Paris, France
[19] INSERM, EMIU 210, Paris, France
[20] Hannover Med Sch, D-3000 Hannover, Germany
[21] Univ Schleswig Holstein, Dept Paediat, Kiel, Germany
[22] Charite Univ Med Berlin, Med Klin 3, Berlin, Germany
来源：
LEUKEMIA | 2006年 / 20卷 / 05期
关键词：
MLL; chromosomal translocations; partner genes; acute leukemia;
D O I：
10.1038/sj.leu.2404150
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：777 / 784
页数：8
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