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@ARTICLE{Grsch:307466,
author = {E. Görsch and S. Rudat and M. Arnone and H. Keppeler and
N. Asokan and J. C. Schröder and T. S. Mills and L. Mix and
L. Kramer and J. Pauluschke-Fröhlich and M. Klimiankou and
J. Weller and G. Klein and C. Lengerke$^*$},
title = {{L}aminin {R}eceptor {C}haracterization in {A}cute
{M}yeloid {L}eukemia: {I}ntegrin α7β1 {D}efines leukemic
cells with {M}igratory {P}otential.},
journal = {Experimental hematology},
volume = {nn},
issn = {0531-5573},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2025-03065},
pages = {nn},
year = {2025},
note = {epub},
abstract = {Interactions with the bone marrow (BM) niche are crucial
for promoting self-renewal and survival of acute myeloid
leukemia (AML) cells. Consequently, AML cells express a
variety of surface receptors to engage with BM niche cells
and extracellular matrix proteins, including laminins.
Despite the association of laminin receptors with stemness
in healthy hematopoiesis, their role in AML remains poorly
understood. In this study, we present a comprehensive
examination of the laminin receptors integrin α3β1,
α6β1, α7β1 and basal cell adhesion molecule (BCAM) in
AML. We demonstrate that high mRNA expression of all four
laminin receptors correlates with poor overall survival.
Notably, integrin α6 and α7 display the highest cell
surface density among the examined laminin receptors and are
higher expressed on AML cells compared to healthy controls.
Moreover, our results indicate that the absence of integrin
α7 expression can identify cells with increased colony
forming potential, even in patients that are negative for
the stem cell marker CD34 usually used to enrich LSC.
Re-analyzing survival data from the TCGA-AML cohort,
integrin α7 expression further allows refinement of the
risk stratification based on the LSC score where low LSC and
integrin α7 levels confer superior survival. Lastly,
integrin α7 appears to mark leukemic cells with enhanced
migratory potential, which can be inhibited by the
anti-integrin α7 blocking antibody in vitro and in vivo.
Together, our results confirm the association of high
laminin receptor expression with poor prognosis, and
establish integrin α7 as marker of high migratory leukemic
cells. TEASER ABSTRACT: Acute myeloid leukemia (AML) cells
engage with supportive bone marrow niche cells and
extracellular matrix (ECM) proteins through surface
receptors. Here, we demonstrate that high mRNA expression of
the laminin receptors integrin α3β1, α6β1, α7β1 and
BCAM correlates with poor overall survival. Moreover,
integrin α7 expression marks leukemic cells displaying
enhanced migratory potential. Together, we believe that our
study significantly advances our understanding of AML-ECM
interactions, and provides important insights that might be
instrumental in the development of future therapies
addressing therapy resistance in AML.},
keywords = {acute myeloid leukemia (Other) / bone marrow niche (Other)
/ integrin α7β1 (Other) / laminin receptors (Other) /
leukemic stem cells (Other) / migration and homing (Other)},
cin = {TU01},
ddc = {610},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41455517},
doi = {10.1016/j.exphem.2025.105363},
url = {https://inrepo02.dkfz.de/record/307466},
}