دورية أكاديمية
Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis
| العنوان: | Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis |
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| المؤلفون: | Jasmine C Wong, Kelley M Weinfurtner, Maria del pilar Alzamora, Scott C Kogan, Michael R Burgess, Yan Zhang, Joy Nakitandwe, Jing Ma, Jinjun Cheng, Shann-Ching Chen, Theodore T Ho, Johanna Flach, Damien Reynaud, Emmanuelle Passegué, James R Downing, Kevin Shannon |
| المصدر: | eLife, Vol 4 (2015) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | monosomy 7, myelodysplastic syndrome, hematopoietic stem cell, haploinsufficiency, oxidative phosphorylation, chromosome engineering, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Chromosome 7 deletions are highly prevalent in myelodysplastic syndrome (MDS) and likely contribute to aberrant growth through haploinsufficiency. We generated mice with a heterozygous germ line deletion of a 2-Mb interval of chromosome band 5A3 syntenic to a commonly deleted segment of human 7q22 and show that mutant hematopoietic cells exhibit cardinal features of MDS. Specifically, the long-term hematopoietic stem cell (HSC) compartment is expanded in 5A3+/del mice, and the distribution of myeloid progenitors is altered. 5A3+/del HSCs are defective for lymphoid repopulating potential and show a myeloid lineage output bias. These cell autonomous abnormalities are exacerbated by physiologic aging and upon serial transplantation. The 5A3 deletion partially rescues defective repopulation in Gata2 mutant mice. 5A3+/del hematopoietic cells exhibit decreased expression of oxidative phosphorylation genes, increased levels of reactive oxygen species, and perturbed oxygen consumption. These studies provide the first functional data linking 7q22 deletions to MDS pathogenesis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/07839; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.07839 |
| URL الوصول: | https://doaj.org/article/22ff762d87894c87b32f30861437c04b |
| رقم الأكسشن: | edsdoj.22ff762d87894c87b32f30861437c04b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.07839 |