Academic Journal
Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies
| العنوان: | Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies |
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| المؤلفون: | Xu, Qingyu, Streuer, Alexander, Jann, Johann-Christoph, Altrock, Eva, Schmitt, Nanni, Flach, Johanna, Sens-Albert, Carla, Rapp, Felicitas, Wolf, Julia, Nowak, Verena, Weimer, Nadine, Obländer, Julia, Palme, Iris, Kuzina, Mariia, Jawhar, Ahmed, Darwich, Ali, Weis, Cleo-Aron, Marx, Alexander, Wuchter, Patrick, Costina, Victor, Jäger, Evelyn, Sperk, Elena, Neumaier, Michael, Fabarius, Alice, Metzgeroth, Georgia, Nolte, Florian, Steiner, Laurenz, Levkin, Pavel A., Jawhar, Mohamad, Hofmann, Wolf-Karsten, Riabov, Vladimir, Nowak, Daniel |
| المصدر: | Nature Communications, 14 (1), Art.-Nr.: 1497 ; ISSN: 2041-1723 |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2023 |
| المجموعة: | KITopen (Karlsruhe Institute of Technologie) |
| مصطلحات موضوعية: | ddc:570, Life sciences, biology, info:eu-repo/classification/ddc/570 |
| الوصف: | Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-1-00-015737-6 1-00-015737-7 |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/001040483800025; info:eu-repo/semantics/altIdentifier/issn/2041-1723; https://publikationen.bibliothek.kit.edu/1000157377; https://publikationen.bibliothek.kit.edu/1000157377/150594009; https://doi.org/10.5445/IR/1000157377 |
| DOI: | 10.5445/IR/1000157377 |
| الاتاحة: | https://publikationen.bibliothek.kit.edu/1000157377 https://publikationen.bibliothek.kit.edu/1000157377/150594009 https://doi.org/10.5445/IR/1000157377 |
| Rights: | https://creativecommons.org/licenses/by/4.0/deed.de ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CB79A170 |
| قاعدة البيانات: | BASE |
| ردمك: | 9781000157376 1000157377 |
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| DOI: | 10.5445/IR/1000157377 |