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@ARTICLE{Pereira:284603,
author = {R. S. Pereira and R. Kumar and A. Cais and L. Paulini and
A. Kahler and J. Bravo and V. R. Minciacchi and T. Krack and
E. Kowarz and C. Zanetti and P. S. Godavarthy and F. Hoeller
and P. Llavona and T. Stark and G. Tascher and D. Nowak and
E. Meduri and B. J. P. Huntly and C. Münch and F. Pampaloni
and R. Marschalek and D. S. Krause$^*$},
title = {{D}istinct and targetable role of calcium-sensing receptor
in leukaemia.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-02023},
pages = {6242},
year = {2023},
abstract = {Haematopoietic stem cells (HSC) reside in the bone marrow
microenvironment (BMM), where they respond to extracellular
calcium [eCa2+] via the G-protein coupled calcium-sensing
receptor (CaSR). Here we show that a calcium gradient exists
in this BMM, and that [eCa2+] and response to [eCa2+] differ
between leukaemias. CaSR influences the location of MLL-AF9+
acute myeloid leukaemia (AML) cells within this niche and
differentially impacts MLL-AF9+ AML versus BCR-ABL1+
leukaemias. Deficiency of CaSR reduces AML leukaemic stem
cells (LSC) 6.5-fold. CaSR interacts with filamin A, a
crosslinker of actin filaments, affects stemness-associated
factors and modulates pERK, β-catenin and c-MYC signaling
and intracellular levels of [Ca2+] in MLL-AF9+ AML cells.
Combination treatment of cytarabine plus CaSR-inhibition in
various models may be superior to cytarabine alone. Our
studies suggest CaSR to be a differential and targetable
factor in leukaemia progression influencing self-renewal of
AML LSC via [eCa2+] cues from the BMM.},
cin = {FM01},
ddc = {500},
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:37802982},
pmc = {pmc:PMC10558580},
doi = {10.1038/s41467-023-41770-0},
url = {https://inrepo02.dkfz.de/record/284603},
}