دورية أكاديمية
CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity
| العنوان: | CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity |
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| المؤلفون: | Julia C. Gutjahr, Elisabeth Bayer, Xiaobing Yu, Julia M. Laufer, Jan P. Höpner, Suzana Tesanovic, Andrea Härzschel, Georg Auer, Tanja Rieß, Astrid Salmhofer, Eva Szenes, Theresa Haslauer, Valerie Durand-Onayli, Andrea Ramspacher, Sandra P. Pennisi, Marc Artinger, Nadja Zaborsky, Alexandre Chigaev, Fritz Aberger, Daniel Neureiter, Lisa Pleyer, Daniel F. Legler, Veronique Orian-Rousseau, Richard Greil, Tanja N. Hartmann |
| المصدر: | Haematologica, Vol 106, Iss 8 (2020) |
| بيانات النشر: | Ferrata Storti Foundation, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell surface. CD44-induced VLA-4 activation could be inhibited by the Src family kinase inhibitor PP2 and the multikinase inhibitor midostaurin. In further consequence, the increased adhesion on VCAM-1 allowed AML cells to strongly bind stromal cells. Thereby VLA-4/VCAM-1 interaction promoted activation of Akt, MAPK, NF-kB and mTOR signaling and decreased AML cell apoptosis. Collectively, our investigations provide a mechanistic description of an unusual CD44 function in regulating VLA-4 avidity in AML, supporting AML cell retention in the supportive BM microenvironment. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/9798; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2019.231944 |
| URL الوصول: | https://doaj.org/article/9bf54160724d40848f05cabcbde9c7ee |
| رقم الأكسشن: | edsdoj.9bf54160724d40848f05cabcbde9c7ee |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2019.231944 |