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

(2016) ONCOTARGET. 7(45). p.73769-73780
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Abstract
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.
Keywords
BCP-ALL, ETV6/RUNX1, LncRNA, CHROMOSOME TRANSLOCATIONS, FUSION PROTEIN, SURVIVAL, TRANSCRIPTION, MECHANISMS, CHILDREN, INSIGHTS, IGF2BP1, TARGET, AML1

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Citation

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MLA
Ghazavi, Farzaneh, Barbara De Moerloose, Wouter Van Loocke, et al. “Unique Long Non-coding RNA Expression Signature in ETV6/RUNX1-driven B-cell Precursor Acute Lymphoblastic Leukemia.” ONCOTARGET 7.45 (2016): 73769–73780. Print.
APA
Ghazavi, F., De Moerloose, B., Van Loocke, W., Wallaert, A., Helsmoortel, H., Ferster, A., Bakkus, M., et al. (2016). Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia. ONCOTARGET, 7(45), 73769–73780.
Chicago author-date
Ghazavi, Farzaneh, Barbara De Moerloose, Wouter Van Loocke, Annelynn Wallaert, Hetty Helsmoortel, Alina Ferster, Marleen Bakkus, et al. 2016. “Unique Long Non-coding RNA Expression Signature in ETV6/RUNX1-driven B-cell Precursor Acute Lymphoblastic Leukemia.” Oncotarget 7 (45): 73769–73780.
Chicago author-date (all authors)
Ghazavi, Farzaneh, Barbara De Moerloose, Wouter Van Loocke, Annelynn Wallaert, Hetty Helsmoortel, Alina Ferster, Marleen Bakkus, Geneviève Plat, Eric Delabesse, Anne Uyttebroeck, Filip Van Nieuwerburgh, Dieter Deforce, Nadine Van Roy, Franki Speleman, Yves Benoit, Tim Lammens, and Pieter Van Vlierberghe. 2016. “Unique Long Non-coding RNA Expression Signature in ETV6/RUNX1-driven B-cell Precursor Acute Lymphoblastic Leukemia.” Oncotarget 7 (45): 73769–73780.
Vancouver
1.
Ghazavi F, De Moerloose B, Van Loocke W, Wallaert A, Helsmoortel H, Ferster A, et al. Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia. ONCOTARGET. 2016;7(45):73769–80.
IEEE
[1]
F. Ghazavi et al., “Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia,” ONCOTARGET, vol. 7, no. 45, pp. 73769–73780, 2016.
@article{8510880,
  abstract     = {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.},
  author       = {Ghazavi, Farzaneh and De Moerloose, Barbara and Van Loocke, Wouter and Wallaert, Annelynn and Helsmoortel, Hetty and Ferster, Alina and Bakkus, Marleen and Plat, Geneviève and Delabesse, Eric and Uyttebroeck, Anne and Van Nieuwerburgh, Filip and Deforce, Dieter and Van Roy, Nadine and Speleman, Franki and Benoit, Yves and Lammens, Tim and Van Vlierberghe, Pieter},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  keywords     = {BCP-ALL,ETV6/RUNX1,LncRNA,CHROMOSOME TRANSLOCATIONS,FUSION PROTEIN,SURVIVAL,TRANSCRIPTION,MECHANISMS,CHILDREN,INSIGHTS,IGF2BP1,TARGET,AML1},
  language     = {eng},
  number       = {45},
  pages        = {73769--73780},
  title        = {Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.18632/oncotarget.12063},
  volume       = {7},
  year         = {2016},
}

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