The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

被引：1267

作者：

Zhang, Jinghui ^{[2
]}

Ding, Li ^{[3
,4
]}

Holmfeldt, Linda ^{[1
]}

Wu, Gang ^{[2
]}

Heatley, Sue L. ^{[1
]}

Payne-Turner, Debbie ^{[1
]}

Easton, John ^{[5
]}

Chen, Xiang ^{[2
]}

Wang, Jianmin ^{[6
]}

Rusch, Michael ^{[2
]}

Lu, Charles ^{[3
]}

Chen, Shann-Ching ^{[1
]}

Wei, Lei ^{[1
]}

Collins-Underwood, J. Racquel ^{[1
]}

Ma, Jing ^{[1
]}

Roberts, Kathryn G. ^{[1
]}

Pounds, Stanley B. ^{[7
]}

Ulyanov, Anatoly ^{[2
]}

Becksfort, Jared ^{[6
]}

Gupta, Pankaj ^{[6
]}

Huether, Robert ^{[2
,8
]}

Kriwacki, Richard W. ^{[8
]}

Parker, Matthew ^{[5
]}

McGoldrick, Daniel J. ^{[6
]}

Zhao, David ^{[6
]}

Alford, Daniel ^{[6
]}

Espy, Stephen ^{[6
]}

Bobba, Kiran Chand ^{[6
]}

Song, Guangchun ^{[1
]}

Pei, Deqing ^{[7
]}

Cheng, Cheng ^{[7
]}

Roberts, Stefan ^{[5
]}

Barbato, Michael I. ^{[5
]}

Campana, Dario ^{[9
]}

Coustan-Smith, Elaine ^{[9
]}

Shurtleff, Sheila A. ^{[1
]}

Raimondi, Susana C. ^{[1
]}

Kleppe, Maria ^{[10
]}

Cools, Jan ^{[10
]}

Shimano, Kristin A. ^{[11
]}

Hermiston, Michelle L. ^{[11
]}

Doulatov, Sergei ^{[12
,13
]}

Eppert, Kolja ^{[12
,13
]}

Laurenti, Elisa ^{[12
,13
]}

Notta, Faiyaz ^{[12
,13
]}

Dick, John E. ^{[12
]}

Basso, Giuseppe ^{[14
]}

Hunger, Stephen P. ^{[15
,16
]}

Loh, Mignon L. ^{[11
]}

Devidas, Meenakshi ^{[17
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA

[3] Washington Univ, Genome Inst, St Louis, MO 63108 USA

[4] Washington Univ, Dept Genet, Sch Med, St Louis, MO 63110 USA

[5] St Jude Childrens Res Hosp, Pediat Canc Genome Project Lab, Memphis, TN 38105 USA

[6] St Jude Childrens Res Hosp, Dept Informat Sci, Memphis, TN 38105 USA

[7] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA

[8] St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA

[9] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[10] Katholieke Univ Leuven, Dept Mol & Dev Genet, Ctr Human Genet, VIB, B-3000 Louvain, Belgium

[11] Univ Calif San Francisco, Dept Pediat, Sch Med, San Francisco, CA 94143 USA

[12] Univ Hlth Network, Dept Stem Cell & Dev Biol, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[13] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[14] Univ Padua, Oncohematol Lab, Dept Pediat, I-35122 Padua, Italy

[15] Univ Colorado, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Aurora, CO 80045 USA

[16] Univ Colorado, Ctr Canc & Blood Disorders, Denver Sch Med, Childrens Hosp Colorado, Aurora, CO 80045 USA

[17] Univ Florida, Dept Biostat, Coll Med, Gainesville, FL 32603 USA

[18] Seattle Childrens Hosp, Dept Lab Med, Seattle, WA 98105 USA

[19] Univ New Mexico, Albuquerque, NM 87131 USA

[20] Univ Virginia, Charlottesville, VA 22903 USA

[21] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA

[22] Washington Univ, Div Oncol, St Louis, MO 63110 USA

[23] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA

来源：

NATURE | 2012年 / 481卷 / 7380期

关键词：

ACTIVATING FLT3 MUTATIONS; RAS; REARRANGEMENT; EXPRESSION; CRLF2; RUNX1; ETV6;

D O I：

10.1038/nature10725

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

引用

页码：157 / 163

页数：7

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