Journal Article

DZNE-2026-00077

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Integrin-dependence of extramedullary erythropoiesis in the spleen of Jak2-V617F positive myeloproliferative neoplasm in mice.

Baldauf, C. K. ; Poschmann, L. ; Edelmann-Stephan, B. ; Angenstein, F.DZNE* ; Haage, T. R. ; Bhuria, V. ; Philipsen, L. ; Berlin, H. ; Dieterich, D. C. ; Böttcher, M. ; Mougiakakos, D. ; Schraven, B. ; Fischer, T.

2026
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.exphem.2025.105340

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.

Keyword(s): Animals (MeSH) ; Janus Kinase 2: genetics (MeSH) ; Janus Kinase 2: metabolism (MeSH) ; Spleen: pathology (MeSH) ; Spleen: metabolism (MeSH) ; Mice (MeSH) ; Myeloproliferative Disorders: genetics (MeSH) ; Myeloproliferative Disorders: pathology (MeSH) ; Myeloproliferative Disorders: metabolism (MeSH) ; Erythropoiesis: genetics (MeSH) ; Integrin alpha4beta1: genetics (MeSH) ; Integrin alpha4beta1: metabolism (MeSH) ; Integrin alpha4beta1: immunology (MeSH) ; CD18 Antigens: genetics (MeSH) ; CD18 Antigens: metabolism (MeSH) ; CD18 Antigens: immunology (MeSH) ; Hematopoiesis, Extramedullary (MeSH) ; Integrin beta1: metabolism (MeSH) ; Integrin beta1: genetics (MeSH) ; Splenomegaly: genetics (MeSH) ; Splenomegaly: pathology (MeSH) ; Erythroblasts: pathology (MeSH) ; Erythroblasts: metabolism (MeSH) ; Janus Kinase 2 ; Jak2 protein, mouse ; Integrin alpha4beta1 ; CD18 Antigens ; Integrin beta1

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Contributing Institute(s):

1. Functional Neuroimaging (AG Angenstein)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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