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@ARTICLE{Ng:283179,
author = {M. Ng and L. Verboon$^*$ and H. Issa$^*$ and R.
Bhayadia$^*$ and M. W. Vermunt$^*$ and R. Winkler$^*$ and L.
Schüler$^*$ and O. Alejo and K. Schuschel$^*$ and E.
Regenyi and D. Borchert and M. Heuser and D. Reinhardt and
M.-L. Yaspo and D. Heckl and J.-H. Klusmann$^*$},
title = {{M}yeloid leukemia vulnerabilities embedded in long
noncoding {RNA} locus {MYNRL}15.},
journal = {iScience},
volume = {26},
number = {10},
issn = {2589-0042},
address = {St. Louis},
publisher = {Elsevier},
reportid = {DKFZ-2023-01958},
pages = {107844},
year = {2023},
abstract = {The noncoding genome presents a largely untapped source of
new biological insights, including thousands of long
noncoding RNA (lncRNA) loci. While lncRNA dysregulation has
been reported in myeloid malignancies, their functional
relevance remains to be systematically interrogated. We
performed CRISPRi screens of lncRNA signatures from normal
and malignant hematopoietic cells and identified MYNRL15 as
a myeloid leukemia dependency. Functional dissection
suggests an RNA-independent mechanism mediated by two
regulatory elements embedded in the locus. Genetic
perturbation of these elements triggered a long-range
chromatin interaction and downregulation of leukemia
dependency genes near the gained interaction sites, as well
as overall suppression of cancer dependency pathways. Thus,
this study describes a new noncoding myeloid leukemia
vulnerability and mechanistic concept for myeloid leukemia.
Importantly, MYNRL15 perturbation caused strong and
selective impairment of leukemia cells of various genetic
backgrounds over normal hematopoietic stem and progenitor
cells in vitro, and depletion of patient-derived xenografts
in vivo.},
keywords = {Biochemistry (Other) / Cancer (Other)},
cin = {FM01},
ddc = {050},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37766974},
pmc = {pmc:PMC10520325},
doi = {10.1016/j.isci.2023.107844},
url = {https://inrepo02.dkfz.de/record/283179},
}