The MLL recombinome of acute leukemias in 2017

被引：512

作者：

Meyer, C. ^{[1
]}

Burmeister, T. ^{[2
]}

Groeger, D. ^{[2
]}

Tsaur, G. ^{[3
]}

Fechina, L. ^{[3
]}

Renneville, A. ^{[4
,5
]}

Sutton, R. ^{[6
]}

Venn, N. C. ^{[6
]}

Emerenciano, M. ^{[7
]}

Pombo-de-Oliveira, M. S. ^{[7
]}

Blunck, C. Barbieri ^{[7
]}

Lopes, B. Almeida ^{[7
]}

Zuna, J. ^{[8
]}

Trka, J. ^{[8
]}

Ballerini, P. ^{[9
]}

Lapillonne, H. ^{[9
]}

De Braekeleer, M. ^{[10
,11
]}

Cazzaniga, G. ^{[12
]}

Abascal, L. Corral ^{[12
]}

van der Velden, V. H. J. ^{[13
]}

Delabesse, E. ^{[14
]}

Park, T. S. ^{[15
]}

Oh, S. H. ^{[16
]}

Silva, M. L. M. ^{[17
]}

Lund-Aho, T. ^{[18
]}

Juvonen, V. ^{[19
,20
,21
]}

Moore, A. S. ^{[22
]}

Heidenreich, O. ^{[23
]}

Vormoor, J. ^{[24
]}

Zerkalenkova, E. ^{[25
]}

Olshanskaya, Y. ^{[25
]}

Bueno, C. ^{[26
,27
,28
]}

Menendez, P. ^{[26
,27
,28
]}

Teigler-Schlegel, A. ^{[29
]}

zur Stadt, U. ^{[30
]}

Lentes, J. ^{[31
]}

Goehring, G. ^{[31
]}

Kustanovich, A. ^{[32
]}

Aleinikova, O. ^{[32
]}

Schafer, B. W. ^{[33
]}

Kubetzko, S. ^{[33
]}

Madsen, H. O. ^{[34
]}

Gruhn, B. ^{[35
]}

Duarte, X. ^{[36
]}

Gameiro, P. ^{[37
]}

Lippert, E. ^{[38
,39
]}

Bidet, A. ^{[38
,39
]}

Cayuela, J. M. ^{[40
]}

Clappier, E. ^{[40
]}

Alonso, C. N. ^{[41
]}

机构：

[1] Goethe Univ, DCAL, Inst Pharmaceut Biology, Max von Laue Str 9, D-60439 Frankfurt, Germany

[2] Charite Dept Hematol Oncol & Tumorimmunol, Berlin, Germany

[3] Ural Fed Univ, Pediat Oncol & Hematol Ctr, Res Inst Med Cell Technol, Reg Children Hosp 1, Ekaterinburg, Russia

[4] CHRU Lille, Lab Hematol Biol & Pathol Ctr, Lille, France

[5] Canc Res Inst Lille, INSERM, UMRS 1172, Lille, France

[6] Uinvers NSW Sydney, Childrens Canc Inst Australia, Sydney, NSW, Australia

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

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

[9] Pierre & Marie Curie Univ, AP HP A Trousseau, Biol Hematol, Paris, France

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

[11] INSERM, U1078, Brest, France

[12] Clin Pediat Univ Milano Bicocca, Ctr Ric Tettamanti, Monza, Italy

[13] Erasmus MC, Dept Immunol, Rotterdam, Netherlands

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

[15] Kyung Hee Univ, Sch Med, Dept Lab Med, Seoul, South Korea

[16] Inje Univ, Coll Med, Dept Lab Med, Busan, South Korea

[17] Natl Canc Inst INCA, Bone Marrow Transplantat Unit, Cytogenet Dept, Rio De Janeiro, Brazil

[18] Fimlab Labs, Lab Clin Genet, Tampere, Finland

[19] Univ Turku, Dept Clin Chem, Turku, Finland

[20] Univ Turku, TYKSLAB, Turku, Finland

[21] Turku Univ, Cent Hosp, Turku, Finland

[22] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia

[23] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England

[24] Newcastle Upon Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Newcastle Upon Tyne, Tyne & Wear, England

[25] Dmitry Rogachev Natl Sci & Pract Ctr Pediat Hemat, Moscow, Russia

[26] Univ Barcelona, Sch Med, Dept Biomed, Josep Carreras Leukemia Res Inst, Barcelona, Spain

[27] ISCIII, CIBER Canc CIBERONC, Madrid, Spain

[28] ICREA, Barcelona, Spain

[29] Inst Pathol, Dept Expt Pathol & Cytol, Giessen, Germany

[30] Univ Med Ctr Hamburg Eppendorf, Ctr Diagnost, Hamburg, Germany

[31] Hannover Med Sch, Dept Human Genet, Hannover, NH, Germany

[32] Belarusian Res Ctr Pediat Oncol Hematol & Immunol, Minsk, BELARUS

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

[34] Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark

[35] Jena Univ Hosp, Dept Pediat, Jena, Germany

[36] Portuguese Inst Oncol Lisbon, Dept Pediat, Lisbon, Portugal

[37] Portuguese Inst Oncol Lisbon, UIPM, Hematooncol Lab, Lisbon, Portugal

[38] Univ Bretagne Occidentale, CHU Brest, Hematol Biol, Brest, France

[39] Univ Bretagne Occidentale, INSERM, U1078, Brest, France

[40] Paris Diderot Univ, AP HP St Louis, Lab Hematol, Paris, France

[41] Hosp Nacl Pediat Prof Dr JP Garrahan, Serv Hematooncol, Buenos Aires, DF, Argentina

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

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

[44] Canc Res Ctr, Tel Aviv, Israel

[45] Tel Aviv Univ, Sackler Med Sch, Tel Aviv, Israel

[46] Southmead Hosp North Bristol NHS Trust, Bristol Genet Lab Pathol Sci, Bristol, Avon, England

[47] Univ Med Ctr Schleswig Holstein, Dept Pediat, Kiel, Germany

[48] MHH, Dept Pediat, Hannover, NH, Germany

[49] Med Univ Vienna, Childrens Canc Res Inst, Vienna, Austria

[50] Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat, Vienna, Austria

来源：

LEUKEMIA | 2018年 / 32卷 / 02期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; FUSION PROTEIN; PROGNOSTIC-SIGNIFICANCE; HISTONE METHYLATION; COMPLEX; CANCER; T(4/11); TRANSLOCATIONS; REARRANGEMENTS;

D O I：

10.1038/leu.2017.213

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：273 / 284

页数：12

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