New insights to the MLL recombinome of acute leukemias

被引：292

作者：

Meyer, C. ^{[1
]}

Kowarz, E. ^{[1
]}

Hofmann, J. ^{[1
]}

Renneville, A. ^{[2
,3
]}

Zuna, J. ^{[4
]}

Trka, J. ^{[4
]}

Ben Abdelali, R. ^{[5
]}

Macintyre, E. ^{[5
]}

De Braekeleer, E. ^{[6
,7
]}

De Braekeleer, M. ^{[6
,7
]}

Delabesse, E. ^{[8
]}

de Oliveira, M. P. ^{[9
]}

Cave, H. ^{[10
]}

Clappier, E. ^{[10
]}

van Dongen, J. J. M. ^{[11
]}

Balgobind, B. V. ^{[12
]}

van den Heuvel-Eibrink, M. M. ^{[12
]}

Beverloo, H. B. ^{[13
]}

Panzer-Gruemayer, R. ^{[14
]}

Teigler-Schlegel, A. ^{[15
]}

Harbott, J. ^{[15
]}

Kjeldsen, E. ^{[16
]}

Schnittger, S. ^{[17
]}

Koehl, U. ^{[18
]}

Gruhn, B. ^{[19
]}

Heidenreich, O. ^{[20
]}

Chan, L. C. ^{[21
]}

Yip, S. F. ^{[21
]}

Krzywinski, M. ^{[22
]}

Eckert, C. ^{[23
]}

Moericke, A. ^{[24
]}

Schrappe, M. ^{[24
]}

Alonso, C. N. ^{[25
]}

Schaefer, B. W. ^{[26
]}

Krauter, J. ^{[27
]}

Lee, D. A. ^{[28
]}

zur Stadt, U. ^{[29
]}

Kronnie, G. Te ^{[30
]}

Sutton, R. ^{[31
]}

Izraeli, S. ^{[32
,33
,34
]}

Trakhtenbrot, L. ^{[32
,33
,34
]}

Lo Nigro, L. ^{[35
]}

Tsaur, G. ^{[36
]}

Fechina, L. ^{[36
]}

Szczepanski, T. ^{[37
]}

Strehl, S. ^{[14
]}

Ilencikova, D. ^{[38
]}

Molkentin, M. ^{[39
]}

Burmeister, T. ^{[39
]}

Dingermann, T. ^{[1
]}

机构：

[1] Univ Frankfurt, Diagnost Ctr Acute Leukemia, Inst Pharmaceut Biol, ZAFES, D-60438 Frankfurt, Germany

[2] CHU Lille, Dept Hematol, Biol & Pathol Ctr, F-59037 Lille, France

[3] INSERM, Team 3, U837, F-59045 Lille, France

[4] Charles Univ Prague, Fac Med 2, Dept Paediat Haematol Oncol, CLIP, Prague, Czech Republic

[5] Univ Paris 05, AP HP Necker, Paris, France

[6] Univ Bretagne Occidentale, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France

[7] INSERM, U613, Brest, France

[8] CHU Purpan, Hematol Lab, Toulouse, France

[9] Inst Nacl Canc Rio de Janeiro, Res Ctr, Pediat Hematol Oncol Program, Rio De Janeiro, Brazil

[10] Hop Robert Debre, Dept Genet, F-75019 Paris, France

[11] Sophia Childrens Univ Hosp, Dept Immunol, Erasmus MC, Rotterdam, Netherlands

[12] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, Rotterdam, Netherlands

[13] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[14] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria

[15] Childrens Univ Hosp, Dept Pediat Hematol & Oncol, Giessen, Germany

[16] Aarhus Univ, Cancercytogenet Lab, Aarhus, Denmark

[17] MLL Munich Leukemia Lab, Munich, Germany

[18] Univ Frankfurt, Dept Pediat Hematol & Oncol, Frankfurt, Germany

[19] Univ Jena, Dept Pediat, Jena, Germany

[20] Univ Newcastle, No Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England

[21] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China

[22] Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[23] Charite, Dept Pediat Oncol & Hematol, CVK, D-13353 Berlin, Germany

[24] Univ Schleswig Holstein, Dept Paediat, Kiel, Germany

[25] Hosp Nacl Pediatria Prof Dr JP Garrahan, Serv Hematooncol, Buenos Aires, DF, Argentina

[26] Univ Childrens Hosp, Dept Oncol, Zurich, Switzerland

[27] Hannover Med Sch, Clin Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany

[28] Univ Texas MD Anderson Canc Ctr, Cell Therapy Sect, Div Pediat, Houston, TX 77030 USA

[29] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[30] Univ Padua, Dept Paediat & Oncohematol, Padua, Italy

[31] Sydney Childrens Hosp, Childrens Canc Inst, Sydney, NSW, Australia

[32] Chaim Sheba Med Ctr, Dept Pediat Hematooncol, Tel Aviv, Israel

[33] Canc Res Ctr, Tel Aviv, Israel

[34] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel

[35] Univ Catania, Ctr Pediat Hematol Oncol, Catania, Italy

[36] Reg Children Hosp 1, Pediat Oncol & Hematol Ctr, Res Inst Med Cell Technol, Ekaterinburg, Russia

[37] Med Univ Silesia, Dept Pediat Hematol & Oncol, Zabrze, Poland

[38] Natl Canc Hosp, Dept Clin Genet, Bratislava, Slovakia

[39] Charite, CBF, Fac Med 3, D-13353 Berlin, Germany

来源：

LEUKEMIA | 2009年 / 23卷 / 08期

关键词：

MLL; translocations partner genes; acute leukemia; ALL; AML; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; CHROMOSOMAL BREAKPOINT SEQUENCES; PARTIAL TANDEM DUPLICATION; MINIMAL-RESIDUAL-DISEASE; HISTONE METHYLATION; PARTNER GENES; PROTEIN; TRANSLOCATIONS; IDENTIFICATION;

D O I：

10.1038/leu.2009.33

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 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. Leukemia (2009) 23, 1490-1499; doi:10.1038/leu.2009.33; published online 5 March 2009

引用

页码：1490 / 1499

页数：10

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