Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia

被引：59

作者：

McKenzie, Mark D. ^{[1
]}

Ghisi, Margherita ^{[2
,23
]}

Oxley, Ethan P. ^{[2
]}

Ngo, Steven ^{[2
]}

Cimmino, Luisa ^{[3
]}

Esnault, Cecile ^{[4
,5
,6
]}

Liu, Ruijie ^{[1
]}

Salmon, Jessica M. ^{[2
]}

Bell, Charles C. ^{[7
,8
]}

Ahmed, Nouraiz ^{[9
]}

Erlichster, Michael ^{[1
,10
]}

Witkowski, Matthew T. ^{[1
,2
,3
,10
]}

Liu, Grace J. ^{[1
,2
,10
]}

Chopin, Michael ^{[11
]}

Dakic, Aleksandar ^{[11
]}

Simankowicz, Emilia ^{[2
]}

Pomilio, Giovanna ^{[2
,12
]}

Vu, Tina ^{[2
]}

Krsmanovic, Pavle ^{[13
]}

Su, Shian ^{[1
]}

Tian, Luyi ^{[1
,10
]}

Baldwin, Tracey M. ^{[1
]}

Zalcenstein, Daniela A. ^{[1
]}

DiRago, Ladina ^{[14
]}

Wang, Shu ^{[15
]}

Metcalf, Donald ^{[10
,14
]}

Johnstone, Ricky W. ^{[7
,8
]}

Croker, Ben A. ^{[15
,16
]}

Lancaster, Graeme I. ^{[17
,18
]}

Murphy, Andrew J. ^{[17
,18
]}

Naik, Shalin H. ^{[1
,10
]}

Nutt, Stephen L. ^{[10
,11
]}

Pospisil, Vitek ^{[13
]}

Schroeder, Timm ^{[9
]}

Wall, Meaghan ^{[10
,19
]}

Dawson, Mark A. ^{[7
,8
]}

Wei, Andrew H. ^{[2
,12
]}

de The, Hugues ^{[4
,5
,6
]}

Ritchie, Matthew E. ^{[1
,10
,20
]}

Zuber, Johannes ^{[21
,22
]}

Dickins, Ross A. ^{[2
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Mol Med Div, 1G Royal Parade, Parkville, Vic 3052, Australia

[2] Monash Univ, Australian Ctr Blood Dis, Commercial Rd, Melbourne, Vic 3004, Australia

[3] NYU, Sch Med, Dept Pathol, 550 1st Ave, New York, NY 10016 USA

[4] PSL Res Univ, Coll France, F-75005 Paris, France

[5] Univ Paris, Inst Rech St Louis, CNRS UMR7212, INSERM U944, F-75010 Paris, France

[6] Hop St Louis, AP HP, Oncol Mol, F-75010 Paris, France

[7] Peter MacCallum Canc Ctr, Melbourne, Vic 3000, Australia

[8] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia

[9] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland

[10] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[11] Walter & Eliza Hall Inst Med Res, Mol Immunol Div, 1G Royal Parade, Parkville, Vic 3052, Australia

[12] Alfred Hosp, Dept Clin Haematol, Melbourne, Vic 3004, Australia

[13] Charles Univ Prague, Fac Med 1, Inst Pathol Physiol & Biocev, Prague, Czech Republic

[14] Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, 1G Royal Parade, Parkville, Vic 3052, Australia

[15] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA

[16] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[17] Baker Heart & Diabet Inst, Melbourne, Vic 3004, Australia

[18] Monash Univ, Dept Immunol & Pathol, Commercial Rd, Melbourne, Vic 3004, Australia

[19] St Vincents Hosp, Victorian Canc Cytogenet Serv, 41 Victoria Parade, Fitzroy, Vic 3065, Australia

[20] Univ Melbourne, Sch Math & Stat, Parkville, Vic 3010, Australia

[21] Res Inst Mol Pathol, Campus Vienna Bioctr 1, A-1030 Vienna, Austria

[22] Med Univ Vienna, A-1030 Vienna, Austria

[23] Ctr Rech Cancerol Toulouse, INSERM U1037, 2 Ave Hubert Curien, F-31037 Toulouse, France

来源：

CELL STEM CELL | 2019年 / 25卷 / 02期

基金：

澳大利亚研究理事会; 英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

TRANSCRIPTION FACTOR PU.1; MONOSOMAL KARYOTYPE; STEM-CELLS; CANCER; GENE; QUANTIFICATION; VISUALIZATION; NEUTROPHILS; ENASIDENIB; INHIBITION;

D O I：

10.1016/j.stem.2019.07.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Tumors are composed of phenotypically heterogeneous cancer cells that often resemble various differentiation states of their lineage of origin. Within this hierarchy, it is thought that an immature subpopulation of tumor-propagating cancer stem cells (CSCs) differentiates into non-tumorigenic progeny, providing a rationale for therapeutic strategies that specifically eradicate CSCs or induce their differentiation. The clinical success of these approaches depends on CSC differentiation being unidirectional rather than reversible, yet this question remains unresolved even in prototypically hierarchical malignancies, such as acute myeloid leukemia (AML). Here, we show in murine and human models of AML that, upon perturbation of endogenous expression of the lineage-determining transcription factor PU.1 or withdrawal of established differentiation therapies, some mature leukemia cells can de-differentiate and reacquire clonogenic and leukemogenic properties. Our results reveal plasticity of CSC maturation in AML, highlighting the need to therapeutically eradicate cancer cells across a range of differentiation states.

引用

页码：258 / +

页数：24

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