Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia

被引：287

作者：

Hong, Dengli ^{[1
]}

Gupta, Rajeev ^{[1
]}

Ancliff, Philip ^{[2
,3
]}

Atzberger, Ann ^{[1
]}

Brown, John ^{[1
]}

Soneji, Shamit ^{[1
]}

Green, Joanne ^{[1
]}

Colman, Sue ^{[6
]}

Piacibello, Wanda ^{[5
]}

Buckle, Veronica ^{[1
]}

Tsuzuki, Shinobu ^{[4
]}

Greaves, Mel ^{[6
]}

Enver, Tariq ^{[1
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC,Mol Haematol Unit, Oxford OX3 9DS, England

[2] Great Ormond St Hosp Sick Children, Dept Haematol, London WC1N 3JH, England

[3] UCL, Inst Child Hlth, Dept Mol Haematol & Canc Biol, London WC1N 3JH, England

[4] Aichi Canc Res Inst, Div Mol Med, Nagoya, Aichi 4648681, Japan

[5] Inst Canc Res & Treatment, Div Res Med Oncol, I-10060 Turin, Italy

[6] Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England

来源：

SCIENCE | 2008年 / 319卷 / 5861期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1126/science.1150648

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：

Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also the cellular framework in which they arise and function. Here we explore the clonal evolution of a form of childhood precursor- B cell acute lymphoblastic leukemia that is characterized by a chromosomal translocation generating a TEL- AML1 fusion gene. We identify a cell compartment in leukemic children that can propagate leukemia when transplanted in mice. By studying a monochorionic twin pair, one preleukemic and one with frank leukemia, we establish the lineal relationship between these "cancer- propagating" cells and the preleukemic cell in which the TEL- AML1 fusion first arises or has functional impact. Analysis of TEL- AML1- transduced cord blood cells suggests that TEL- AML1 functions as a first- hit mutation by endowing this preleukemic cell with altered self- renewal and survival properties.

引用

页码：336 / 339

页数：4

共 9 条

[1] Prospective identification of tumorigenic breast cancer cells
Al-Hajj, M
Wicha, MS
Benito-Hernandez, A
Morrison, SJ
Clarke, MF
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) : 3983 - 3988
[2] Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
Bonnet, D
Dick, JE
[J]. NATURE MEDICINE, 1997, 3 (07) : 730 - 737
[3] Leukemia in twins: lessons in natural history
Greaves, MF
Maia, AT
Wiemels, JL
Ford, AM
[J]. BLOOD, 2003, 102 (07) : 2321 - 2333
[4] Tumor growth need not be driven by rare cancer stem cells
Kelly, Priscilla N.
Dakic, Aleksandar
Adams, Jerry M.
Nutt, Stephen L.
Strasser, Andreas
[J]. SCIENCE, 2007, 317 (5836) : 337 - 337
[5] Identification of bronchioalveolar stem cells in normal lung and lung cancer
Kim, CFB
Jackson, EL
Woolfenden, AE
Lawrence, S
Babar, I
Vogel, S
Crowley, D
Bronson, RT
Jacks, T
[J]. CELL, 2005, 121 (06) : 823 - 835
[6] A human colon cancer cell capable of initiating tumour growth in immunodeficient mice
O'Brien, Catherine A.
Pollett, Aaron
Gallinger, Steven
Dick, John E.
[J]. NATURE, 2007, 445 (7123) : 106 - 110
[7] Shurtleff SA, 1995, LEUKEMIA, V9, P1985
[8] Identification of human brain tumour initiating cells
Singh, SK
Hawkins, C
Clarke, ID
Squire, JA
Bayani, J
Hide, T
Henkelman, RM
Cusimano, MD
Dirks, PB
[J]. NATURE, 2004, 432 (7015) : 396 - 401
[9] Cancer stem cells: lessons from leukemia
Wang, JCY
Dick, JE
[J]. TRENDS IN CELL BIOLOGY, 2005, 15 (09) : 494 - 501

← 1 →