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@ARTICLE{Baldauf:284042,
author = {Baldauf, Conny K and Poschmann, Linda and Edelmann-Stephan,
Bärbel and Angenstein, Frank and Haage, Tobias R and
Bhuria, Vikas and Philipsen, Lars and Berlin, Hannes and
Dieterich, Daniela C and Böttcher, Martin and Mougiakakos,
Dimitrios and Schraven, Burkhart and Fischer, Thomas},
title = {{I}ntegrin-dependence of extramedullary erythropoiesis in
the spleen of {J}ak2-{V}617{F} positive myeloproliferative
neoplasm in mice.},
journal = {Experimental hematology},
volume = {154},
issn = {0531-5573},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DZNE-2026-00077},
pages = {105340},
year = {2026},
abstract = {The molecular mechanisms driving splenomegaly in
myeloproliferative neoplasms (MPNs) remain poorly
understood. Utilizing the Jak2-V617F knock-in mouse model,
we investigated the role of β1- and β2-integrins in
regulating spleen volume and spleen weight. The response to
neutralizing antibodies against VLA-4 and the β2-integrin
chain, as well as to isotype controls, was evaluated by
serial intraindividual magnetic resonance imaging, by
assessment of spleen weight and by analysis of the cellular
composition of spleens. Short-term anti-VLA-4/β2-integrin
treatment (applied on day 1 and evaluated at day 8)
significantly reduced the spleen volume by $30\%$ compared
with the immunoglobulin G (IgG) control. At the cellular
level, anti-integrin treatment led to a substantial $30\%$
decrease in erythroblast counts and a $23\%$ reduction in
basophilic erythroblasts within the spleen, as compared with
the isotype control. Furthermore, immunohistochemistry
analysis of spleen sections revealed that CD71 (=
Transferrin receptor protein 1) expression in spleen
remained largely unchanged, whereas there was a clear
reduction in Ter119 expression upon anti-integrin treatment.
These data suggest that the substantial decrease in
erythroblasts following anti-integrin treatment is a primary
factor contributing to the overall reduction in spleen size.
To study the spleen architecture, multiepitope ligand
cartography (MELC) analysis of spleen sections was applied.
This demonstrated that the spatial distribution of the
marginal zone, red pulp, and white pulp remained unaltered
upon anti-integrin treatment in JAK2-V617F knock-in mice. In
summary, the present study identified a previously
unrecognized role of the β1-integrin VLA-4 and of
β2-integrin chains in extramedullary erythropoiesis of the
spleen in JAK2-V617F-induced disease.},
keywords = {Animals / Janus Kinase 2: genetics / Janus Kinase 2:
metabolism / Spleen: pathology / Spleen: metabolism / Mice /
Myeloproliferative Disorders: genetics / Myeloproliferative
Disorders: pathology / Myeloproliferative Disorders:
metabolism / Erythropoiesis: genetics / Integrin
alpha4beta1: genetics / Integrin alpha4beta1: metabolism /
Integrin alpha4beta1: immunology / CD18 Antigens: genetics /
CD18 Antigens: metabolism / CD18 Antigens: immunology /
Hematopoiesis, Extramedullary / Integrin beta1: metabolism /
Integrin beta1: genetics / Splenomegaly: genetics /
Splenomegaly: pathology / Erythroblasts: pathology /
Erythroblasts: metabolism / Janus Kinase 2 (NLM Chemicals) /
Jak2 protein, mouse (NLM Chemicals) / Integrin alpha4beta1
(NLM Chemicals) / CD18 Antigens (NLM Chemicals) / Integrin
beta1 (NLM Chemicals)},
cin = {AG Angenstein},
ddc = {610},
cid = {I:(DE-2719)1310004},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41360369},
doi = {10.1016/j.exphem.2025.105340},
url = {https://pub.dzne.de/record/284042},
}