Clonal Evolution of Preleukemic Hematopoietic Stem Cells Precedes Human Acute Myeloid Leukemia

被引：546

作者：

Jan, Max ^{[1
,2
]}

Snyder, Thomas M. ^{[3
,4
]}

Corces-Zimmerman, M. Ryan ^{[1
,2
]}

Vyas, Paresh ^{[5
,6
,7
,8
]}

Weissman, Irving L. ^{[1
,2
]}

Quake, Stephen R. ^{[3
,4
]}

Majeti, Ravindra ^{[1
,2
,9
]}

机构：

[1] Stanford Univ, Sch Med, Program Canc Biol, Canc Inst,Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94305 USA

[2] Stanford Univ, Sch Med, Ludwig Ctr, Palo Alto, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Bioengn, Palo Alto, CA 94305 USA

[4] Stanford Univ, Sch Med, Howard Hughes Med Inst, Palo Alto, CA 94305 USA

[5] Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DS, England

[6] Weatherall Inst Mol Med, Dept Haematol, Oxford OX3 9DS, England

[7] Univ Oxford, Oxford OX3 9DS, England

[8] Oxford Univ Hosp NHS Trust, Oxford OX3 9DS, England

[9] Stanford Univ, Sch Med, Dept Internal Med, Div Hematol, Palo Alto, CA 94305 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2012年 / 4卷 / 149期

关键词：

METHYLTRANSFERASE GENE EZH2; ACUTE MYELOGENOUS LEUKEMIA; DNA-SEQUENCING DATA; MYELODYSPLASTIC SYNDROMES; LYMPHOBLASTIC-LEUKEMIA; INITIATING CELLS; SELF-RENEWAL; MUTATIONS; GENOME; TET2;

D O I：

10.1126/scitranslmed.3004315

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Given that most bone marrow cells are short-lived, the accumulation of multiple leukemogenic mutations in a single clonal lineage has been difficult to explain. We propose that serial acquisition of mutations occurs in self-renewing hematopoietic stem cells (HSCs). We investigated this model through genomic analysis of HSCs from six patients with de novo acute myeloid leukemia (AML). Using exome sequencing, we identified mutations present in individual AML patients harboring the FLT3-ITD (internal tandem duplication) mutation. We then screened the residual HSCs and detected some of these mutations including mutations in the NPM1, TET2, and SMC1A genes. Finally, through single-cell analysis, we determined that a clonal progression of multiple mutations occurred in the HSCs of some AML patients. These preleukemic HSCs suggest the clonal evolution of AML genomes from founder mutations, revealing a potential mechanism contributing to relapse. Such preleukemic HSCs may constitute a cellular reservoir that should be targeted therapeutically for more durable remissions.

引用

页数：10

共 46 条

[1] Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies [J].

Abdel-Wahab, Omar ;

Mullally, Ann ;

Hedvat, Cyrus ;

Garcia-Manero, Guillermo ;

Patel, Jay ;

Wadleigh, Martha ;

Malinge, Sebastien ;

Yao, JinJuan ;

Kilpivaara, Outi ;

Bhat, Rukhmi ;

Huberman, Kety ;

Thomas, Sabrena ;

Dolgalev, Igor ;

Heguy, Adriana ;

Paietta, Elisabeth ;

Le Beau, Michelle M. ;

Beran, Miloslav ;

Tallman, Martin S. ;

Ebert, Benjamin L. ;

Kantarjian, Hagop M. ;

Stone, Richard M. ;

Gilliland, D. Gary ;

Crispino, John D. ;

Levine, Ross L. .

BLOOD, 2009, 114 (01) :144-147

[2] Glycogen synthase kinase 3β missplicing contributes to leukemia stem cell generation [J].

Abrahamsson, Annelie E. ;

Geron, Ifat ;

Gotlib, Jason ;

Dao, Kim-Hien T. ;

Barroga, Charlene F. ;

Newton, Isabel G. ;

Giles, Francis J. ;

Durocher, Jeffrey ;

Creusot, Remi S. ;

Karimi, Mobin ;

Jones, Carol ;

Zehnder, James L. ;

Keating, Armand ;

Negrin, Robert S. ;

Weissman, Irving L. ;

Jamieson, Catriona H. M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (10) :3925-3929

[3] Genetic variegation of clonal architecture and propagating cells in leukaemia [J].

Anderson, Kristina ;

Lutz, Christoph ;

van Delft, Frederik W. ;

Bateman, Caroline M. ;

Guo, Yanping ;

Colman, Susan M. ;

Kempski, Helena ;

Moorman, Anthony V. ;

Titley, Ian ;

Swansbury, John ;

Kearney, Lyndal ;

Enver, Tariq ;

Greaves, Mel .

NATURE, 2011, 469 (7330) :356-+

[4] Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers [J].

Barber, Thomas D. ;

McManus, Kirk ;

Yuen, Karen W. Y. ;

Reis, Marcelo ;

Parmigiani, Giovanni ;

Shen, Dong ;

Barrett, Irene ;

Nouhi, Yasaman ;

Spencer, Forrest ;

Markowitz, Sanford ;

Velculescu, Victor E. ;

Kinzler, Kenneth W. ;

Vogelstein, Bert ;

Lengauer, Christoph ;

Hieter, Philip .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (09) :3443-3448

[5] Genetic diagnosis by whole exome capture and massively parallel DNA sequencing [J].

Choi, Murim ;

Scholl, Ute I. ;

Ji, Weizhen ;

Liu, Tiewen ;

Tikhonova, Irina R. ;

Zumbo, Paul ;

Nayir, Ahmet ;

Bakkaloglu, Aysin ;

Ozen, Seza ;

Sanjad, Sami ;

Nelson-Williams, Carol ;

Farhi, Anita ;

Mane, Shrikant ;

Lifton, Richard P. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (45) :19096-19101

[6] Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples [J].

Cloos, J. ;

Goemans, B. F. ;

Hess, C. J. ;

van Oostveen, J. W. ;

Waisfisz, Q. ;

Corthals, S. ;

de lange, D. ;

Boeckx, N. ;

Hahlen, K. ;

Reinhardt, D. ;

Creutzig, U. ;

Schuurhuis, G. J. ;

Zwaan, Ch M. ;

Kaspers, G. J. L. .

LEUKEMIA, 2006, 20 (07) :1217-1220

[7] Mutation in TET2 in Myeloid Cancers [J].

Delhommeau, Francois ;

Dupont, Sabrina ;

Della Valle, Veronique ;

James, Chloe ;

Trannoy, Severine ;

Masse, Aline ;

Kosmider, Olivier ;

Le Couedic, Jean-Pierre ;

Robert, Fabienne ;

Alberdi, Antonio ;

Lecluse, Yann ;

Plo, Isabelle ;

Dreyfus, Francois J. ;

Marzac, Christophe ;

Casadevall, Nicole ;

Lacombe, Catherine ;

Romana, Serge P. ;

Dessen, Philippe ;

Soulier, Jean ;

Viguie, Franck ;

Fontenay, Michaela ;

Vainchenker, William ;

Bernard, Olivier A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (22) :2289-2301

[8] A framework for variation discovery and genotyping using next-generation DNA sequencing data [J].

DePristo, Mark A. ;

Banks, Eric ;

Poplin, Ryan ;

Garimella, Kiran V. ;

Maguire, Jared R. ;

Hartl, Christopher ;

Philippakis, Anthony A. ;

del Angel, Guillermo ;

Rivas, Manuel A. ;

Hanna, Matt ;

McKenna, Aaron ;

Fennell, Tim J. ;

Kernytsky, Andrew M. ;

Sivachenko, Andrey Y. ;

Cibulskis, Kristian ;

Gabriel, Stacey B. ;

Altshuler, David ;

Daly, Mark J. .

NATURE GENETICS, 2011, 43 (05) :491-+

[9] Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing [J].

Ding, Li ;

Ley, Timothy J. ;

Larson, David E. ;

Miller, Christopher A. ;

Koboldt, Daniel C. ;

Welch, John S. ;

Ritchey, Julie K. ;

Young, Margaret A. ;

Lamprecht, Tamara ;

McLellan, Michael D. ;

McMichael, Joshua F. ;

Wallis, John W. ;

Lu, Charles ;

Shen, Dong ;

Harris, Christopher C. ;

Dooling, David J. ;

Fulton, Robert S. ;

Fulton, Lucinda L. ;

Chen, Ken ;

Schmidt, Heather ;

Kalicki-Veizer, Joelle ;

Magrini, Vincent J. ;

Cook, Lisa ;

McGrath, Sean D. ;

Vickery, Tammi L. ;

Wendl, Michael C. ;

Heath, Sharon ;

Watson, Mark A. ;

Link, Daniel C. ;

Tomasson, Michael H. ;

Shannon, William D. ;

Payton, Jacqueline E. ;

Kulkarni, Shashikant ;

Westervelt, Peter ;

Walter, Matthew J. ;

Graubert, Timothy A. ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

DiPersio, John F. .

NATURE, 2012, 481 (7382) :506-510

[10] Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders [J].

Ernst, Thomas ;

Chase, Andrew J. ;

Score, Joannah ;

Hidalgo-Curtis, Claire E. ;

Bryant, Catherine ;

Jones, Amy V. ;

Waghorn, Katherine ;

Zoi, Katerina ;

Ross, Fiona M. ;

Reiter, Andreas ;

Hochhaus, Andreas ;

Drexler, Hans G. ;

Duncombe, Andrew ;

Cervantes, Francisco ;

Oscier, David ;

Boultwood, Jacqueline ;

Grand, Francis H. ;

Cross, Nicholas C. P. .

NATURE GENETICS, 2010, 42 (08) :722-U109

← 1 2 3 4 5 →