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Total paired-end RNA sequencing of bone marrow and peripheral blood MNCs from patients with Juvenile myelomonocytic leukemia and age-matched controls

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147523 | GEO | 2021/01/27

REPOSITORIES: GEO

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