Coexistence of LMPP-like and GMP-like Leukemia Stem Cells in Acute Myeloid Leukemia

被引：488

作者：

Goardon, Nicolas ^{[1
]}

Marchi, Emanuele ^{[1
]}

Atzberger, Ann ^{[1
]}

Quek, Lynn ^{[1
]}

Schuh, Anna ^{[2
]}

Soneji, Shamit ^{[1
]}

Woll, Petter ^{[3
]}

Mead, Adam ^{[3
]}

Alford, Kate A. ^{[1
]}

Rout, Raj ^{[4
]}

Chaudhury, Salma ^{[4
]}

Gilkes, Amanda ^{[5
]}

Knapper, Steve ^{[5
]}

Beldjord, Kheira ^{[6
,7
]}

Begum, Suriya ^{[8
]}

Rose, Susan ^{[8
]}

Geddes, Nicola ^{[8
]}

Griffiths, Mike ^{[8
]}

Standen, Graham ^{[9
]}

Sternberg, Alexander ^{[10
]}

Cavenagh, Jamie ^{[11
]}

Hunter, Hannah ^{[12
]}

Bowen, David ^{[13
]}

Killick, Sally ^{[14
]}

Robinson, Lisa ^{[15
]}

Price, Andrew ^{[4
]}

Macintyre, Elizabeth ^{[6
,7
]}

Virgo, Paul ^{[16
]}

Burnett, Alan ^{[5
]}

Craddock, Charles ^{[17
,18
]}

Enver, Tariq ^{[1
]}

Jacobsen, Sten Eirik W. ^{[3
]}

Porcher, Catherine ^{[1
]}

Vyas, Paresh ^{[1
,2
]}

机构：

[1] Univ Oxford, WIMM, MRC MHU, Oxford OX3 9DS, England

[2] Oxford Radcliffe Hosp NHS Trust, Dept Haematol, Oxford OX3 9DU, England

[3] Univ Oxford, WIMM, HSCB, Oxford OX3 9DS, England

[4] Nuffield Orthoped Hosp, Nuffield Dept Orthoped, Oxford OX3 7LD, England

[5] Cardiff Univ, Coll Med, Dept Haematol, Cardiff CF14 4XN, S Glam, Wales

[6] Univ Paris 05, Hop Necker Enfants Malad, AP HP, CNRS,UMR 8147, F-75015 Paris, France

[7] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Dept Haematol, F-75015 Paris, France

[8] W Midlands Reg Cytogenet Lab, Birmingham B15 2TG, W Midlands, England

[9] Bristol Royal Infirm & Gen Hosp, Bristol BS2 8HW, Avon, England

[10] Great Western Hosp, Dept Haematol, Swindon SN3 6BB, Wilts, England

[11] St Bartholomews Hosp, Dept Haematol, London EC1A 7BE, England

[12] Plymouth Hosp, Dept Haematol, Plymouth PL6 8DH, Devon, England

[13] Dept Haematol, Leeds LS9 7TF, W Yorkshire, England

[14] Bournemouth Hosp, Dept Haematol, Bournemouth BH7 7DW, Dorset, England

[15] Hereford Hosp, Dept Haematol, Hereford HR1 2BN, England

[16] N Bristol NHS Trust, Dept Immunol, Bristol BS10 5NB, Avon, England

[17] Univ Birmingham, Dept Haematol, Birmingham B15 2TH, W Midlands, England

[18] Univ Hosp Birmingham, Birmingham B15 2TH, W Midlands, England

来源：

CANCER CELL | 2011年 / 19卷 / 01期

关键词：

MULTIPOTENT HEMATOPOIETIC PROGENITORS; LINEAGE COMMITMENT; INITIATING CELLS; IN-VITRO; HIERARCHY; EXPRESSION; IDENTIFICATION; BLOOD; VIVO; MAP;

D O I：

10.1016/j.ccr.2010.12.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The relationships between normal and leukemic stem/progenitor cells are unclear. We show that in similar to 80% of primary human CD34(+) acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. Both populations have leukemic stem cell (LSC) activity and are hierarchically ordered; one LSC population gives rise to the other. Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). This suggests that in most cases primary CD34(+) AML is a progenitor disease where LSCs acquire abnormal self-renewal potential.

引用

页码：138 / 152

页数：15

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