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Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes

ABSTRACT: Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes

PROVIDER: PRJNA494085 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7945490_1.fastq.gz	Fastqsanger.gz
	SRR7945490_2.fastq.gz	Fastqsanger.gz
	SRR7945500_1.fastq.gz	Fastqsanger.gz
	SRR7945500_2.fastq.gz	Fastqsanger.gz
	SRR7945510_1.fastq.gz	Fastqsanger.gz

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Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes

Project description:Very long intergenic non-coding RNAs (vlincRNAs) are a novel class of long transcripts (~50 kb to 1 Mb) with cell type- or cancer-specific expression. We report the discovery and characterization of 256 vlincRNAs from a cohort of 64 primary childhood pre-B and pre-T acute lymphoblastic leukemia (cALL) samples, of which 61% are novel and specifically expressed in cALL. Validation was performed in 35 pre-B and pre-T cALL primary samples. We show that their expression is cALL immunophenotype and molecular subtype-specific and correlated with epigenetic modifications on their promoters, much like protein-coding genes. While the biological functions of these vlincRNAs’s are still unknown, our results suggest they could play a role in cALL etiology or progression. Please note that the study consists of investigating very long intergenic non coding RNAs (vlincRNAs) in childhood acute lymphoblastic leukemia. The study primarily uses RNA-seq data (GSE89071) with the current additional epigenetic data that is specific to this study (chip-seq and wgb-seq).

2018-10-15 | GSE120677 | GEO

Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes.

Project description:Very long intergenic non-coding RNAs (vlincRNAs) are a novel class of long transcripts (~50 kb to 1 Mb) with cell type- or cancer-specific expression. We report the discovery and characterization of 256 vlincRNAs from a cohort of 64 primary childhood pre-B and pre-T acute lymphoblastic leukemia (cALL) samples, of which 61% are novel and specifically expressed in cALL. Validation was performed in 35 pre-B and pre-T cALL primary samples. We show that their expression is cALL immunophenotype and molecular subtype-specific and correlated with epigenetic modifications on their promoters, much like protein-coding genes. While the biological functions of these vlincRNAs are still unknown, our results suggest they could play a role in cALL etiology or progression.

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Proteomics analysis of childhood acute lymphoblastic leukemia cell lines reveals novel drug vulnerabilities

Project description:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and it has a 5-year survival rate of 85% for European children. But for subsets of patients who fail to respond to standard of care chemotherapeutics, treatment options are limited, and clinical prognosis is poor. To establish a platform and methodology to better characterize ALL subtypes and identify their pharmacologic vulnerabilities, we assembled a biobank of 49 readily available childhood ALL cell lines representing diverse immunotypes and genetic profiles. Using these cell lines, we performed comprehensive multi-omic analyses, providing proteomic, transcriptomic and pharmacoproteomic characterization of childhood ALL. We used this resource to characterize the functional impact of genetic fusions and cellular differentiation states on the proteome. Additionally, we identified a novel drug vulnerability in one of the ALL subtypes. Our results are provided as an interactive online data portal with navigable proteomics, transcriptomics, and drug sensitivity profiles.

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Project description:Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared to late relapsed disease. The vast majority of genes was up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G/2M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis. Keywords: disease state analysis

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Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia

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Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans

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