miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

被引：74

作者：

Kotani, Ai ^{[1
,2
]}

Ha, Daon ^{[3
]}

Hsieh, James ^{[4
]}

Rao, Prakash K. ^{[1
]}

Schotte, Diana ^{[5
]}

den Boer, Monique L. ^{[5
]}

Armstrong, Scott A. ^{[6
,7
]}

Lodish, Harvey F. ^{[1
,3
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Mol Therapy, Tokyo, Japan

[3] MIT, Dept Biol, Cambridge, MA 02139 USA

[4] Washington Univ, Sch Med, Dept Med, Siteman Canc Ctr, St Louis, MO 63110 USA

[5] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands

[6] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA USA

来源：

BLOOD | 2009年 / 114卷 / 19期

基金：

日本学术振兴会; 美国国家卫生研究院;

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; LET-7; MICRORNA; MESSENGER-RNA; FUSION GENE; MLL; RESISTANCE; PROLIFERATION; P27(KIP1); CLEAVAGE;

D O I：

10.1182/blood-2008-12-191619

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL. (Blood. 2009; 114:4169-4178)

引用

页码：4169 / 4178

页数：10

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