Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia

被引：30

作者：

Ghazavi, Farzaneh ^{[1
,2
]}

De Moerloose, Barbara ^{[1
]}

Van Loocke, Wouter ^{[2
]}

Wallaert, Annelynn ^{[2
]}

Helsmoortel, Hetty H. ^{[1
,2
]}

Ferster, Alina ^{[3
]}

Bakkus, Marleen ^{[4
]}

Plat, Genevieve ^{[5
]}

Delabesse, Eric ^{[6
]}

Uyttebroeck, Anne ^{[7
]}

Van Nieuwerburgh, Filip ^{[8
]}

Deforce, Dieter ^{[8
]}

Van Roy, Nadine ^{[2
]}

Speleman, Frank ^{[2
]}

Benoit, Yves ^{[1
]}

Lammens, Tim ^{[1
]}

Van Vlierberghe, Pieter ^{[2
]}

机构：

[1] Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Ghent, Belgium

[2] Ghent Univ Hosp, Dept Paediat & Genet, Ctr Med Genet, Ghent, Belgium

[3] Univ Libre Bruxelles, HUDERF, Dept Hematooncol, Brussels, Belgium

[4] VUB, Univ Hosp Brussels, Dept Hematol, Brussels, Belgium

[5] Childrens Hosp, Dept Hematol, Toulouse, France

[6] Univ Toulouse 3, Inst Univ Cancerol Toulouse, Dept Hematol, Toulouse, France

[7] Univ Hosp Leuven, Dept Pediat Hematooncol, Leuven, Belgium

[8] Univ Ghent, Dept Pharmaceut, Lab Pharmaceut Biotechnol, Ghent, Belgium

来源：

ONCOTARGET | 2016年 / 7卷 / 45期

关键词：

BCP-ALL; ETV6/RUNX1; LncRNA; CHROMOSOME TRANSLOCATIONS; FUSION PROTEIN; SURVIVAL; MECHANISMS; TRANSCRIPT; INSIGHTS; IGF2BP1; SET;

D O I：

10.18632/oncotarget.12063

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Overwhelming evidence indicates that long non-coding RNAs have essential roles in tumorigenesis. Nevertheless, their role in the molecular pathogenesis of pediatric B-cell precursor acute lymphoblastic leukemia has not been extensively explored. Here, we conducted a comprehensive analysis of the long non-coding RNA transcriptome in ETV6/RUNX1-positive BCP-ALL, one of the most frequent subtypes of pediatric leukemia. First, we used primary leukemia patient samples to identify an ETV6/RUNX1 specific expression signature consisting of 596 lncRNA transcripts. Next, integration of this lncRNA signature with RNA sequencing of BCP-ALL cell lines and lncRNA profiling of an in vitro model system of ETV6/RUNX1 knockdown, revealed that lnc-NKX2-3-1, lnc-TIMM21-5, lnc-ASTN1-1 and lnc-RTN4R-1 are truly regulated by the oncogenic fusion protein. Moreover, sustained inactivation of lnc-RTN4R-1 and lnc-NKX2-3-1 in ETV6/RUNX1 positive cells caused profound changes in gene expression. All together, our study defined a unique lncRNA expression signature associated with ETV6/RUNX1-positive BCP-ALL and identified lnc-RTN4R-1 and lnc-NKX2-3-1 as lncRNAs that might be functionally implicated in the biology of this prevalent subtype of human leukemia.

引用

页码：73769 / 73780

页数：12

共 40 条

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