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Series GSE147523 Query DataSets for GSE147523
Status Public on Jan 27, 2021
Title Total paired-end RNA sequencing of bone marrow and peripheral blood MNCs from patients with Juvenile myelomonocytic leukemia and age-matched controls
Organism Homo sapiens
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Dysregulation of the non-coding RNA transcriptome has been demonstrated in Juvenile myelomonocytic leukemia (JMML), a rare and aggressive disorder of early childhood. Currently, JMML treatment relies on hematopoietic stem cell transplantation resulting in long-term overall survival of only 50-60%. Consequently, there is need to develop novel treatments. In this study we investigated the therapeutic potential of targeting overexpressed long non-coding RNAs (lncRNAs) in JMML. Total RNA sequencing from 19 previously untreated JMML patients and 3 pediatric normal bone marrow samples revealed 202 differentially expressed lncRNA genes (144 upregulated and 58 downregulated). Molecular knockdown (≥ 70% compared to mock control) after 24h of incubation was observed for 6 out of 10 overexpressed lncRNAs for which LNA GapmeRs were designed. For 3 lncRNAs (lnc-THADA-4-1, lnc-ACOT9-1 and NRIR) knockdown resulted in a significant effect on cell viability after 96h or 72h of incubation in cell lines or in primary JMML cells, respectively. Importantly, the extend of cellular damage correlated well with the expression of the lncRNA of interest. In conclusion, we provided proof-of-concept that knockdown of overexpressed lncRNAs such as lnc-THADA-4-1, lnc-ACOT9-1 and NRIR is a feasible therapeutic strategy in vitro in haematopoietic cell lines and in primary JMML cells. These results will need further validation in JMML xenograft models.
Overall design We report long non-coding RNA transcriptome in patients with Juvenile Myelomonocytic Leukemia. To this end, total paired-end RNA sequencing identified 38117 non-coding RNA genes of which 202 differentially expressed between JMML and age-matched healthy controls.
Examination of total paired-end RNA sequencing data between bone marrow and peripheral blood MNCs from JMML and bone marrow MNCs from healthy age-matched controls.
Contributor(s) Hofmans M, Lammens T, Philippé J, DeMoerloose B
Citation(s) 33490078, 33531590
Submission date Mar 25, 2020
Last update date Feb 08, 2021
Contact name Mattias Hofmans
Organization name Ghent University Hospital
Department Department of pediatrics
Lab Pediatric Hematology-Oncology and Stem Cell Transplantation
Street address C. Heymanslaan 10
City Gent
ZIP/Postal code 9000
Country Belgium
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (22)
GSM4432517 K17/3535
GSM4432518 K17/3539
GSM4432519 K17/3541
BioProject PRJNA615164
SRA SRP254013

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Supplementary file Size Download File type/resource
GSE147523_normalizedCounts_Deseq2.txt.gz 4.9 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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