PML targeting eradicates quiescent leukaemia-initiating cells

被引：449

作者：

Ito, Keisuke ^{[1
,2
,4
,5
]}

Bernardi, Rosa ^{[1
,2
,4
,5
]}

Morotti, Alessandro ^{[1
,2
,4
,5
]}

Matsuoka, Sahoko ^{[6
]}

Saglio, Giuseppe ^{[7
]}

Ikeda, Yasuo ^{[6
]}

Rosenblatt, Jacalyn ^{[3
]}

Avigan, David E. ^{[3
]}

Teruya-Feldstein, Julie ^{[5
]}

Pandolfi, Pier Paolo ^{[1
,2
,4
,5
]}

机构：

[1] Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Pathol, Boston, MA 02215 USA

[3] Harvard Univ, Sch Med, Div Hematol & Oncol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[4] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA

[6] Keio Univ, Sch Med, Div Hematol, Dept Internal Med,Shinjuku Ku, Tokyo 1608582, Japan

[7] Univ Turin, Div Hematol & Internal Med, Dept Clin & Biol Sci, I-10043 Turin, Italy

来源：

NATURE | 2008年 / 453卷 / 7198期

关键词：

D O I：

10.1038/nature07016

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：

The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.

引用

页码：1072 / U4

页数：8

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