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Bayley, Rachel, Blakemore, Daniel, Cancian, Laila, Dumon, Stephanie, Volpe, Giacomo, Ward, Carl, Almaghrabi, Ruba, Gujar, Jidnyasa, Reeve, Natasha, Raghavan, Manoj, Higgs, Martin R, Stewart, Grant S, Petermann, Eva and García, Paloma (2018) MYBL2 Supports DNA Double Strand Break Repair in Hematopoietic Stem Cells. Cancer research, 78 (20). pp. 5767-5779. ISSN 1538-7445. This article is available to all UHB staff and students login using a UHB Athens Account. Register for Athens here - https://openathens.nice.org.uk/
Full text not available from this repository.Abstract
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by blood cytopenias that occur as a result of somatic mutations in hematopoietic stem cells (HSC). MDS leads to ineffective hematopoiesis, and as many as 30% of patients progress to acute myeloid leukemia (AML). The mechanisms by which mutations accumulate in HSC during aging remain poorly understood. Here we identify a novel role for MYBL2 in DNA double-strand break (DSB) repair in HSC. In patients with MDS, low levels associated with and preceded transcriptional deregulation of DNA repair genes. Stem/progenitor cells from these patients display dysfunctional DSB repair kinetics after exposure to ionizing radiation (IR). Haploinsufficiency of in mice also led to a defect in the repair of DSBs induced by IR in HSC and was characterized by unsustained phosphorylation of the ATM substrate KAP1 and telomere fragility. Our study identifies MYBL2 as a crucial regulator of DSB repair and identifies expression levels as a potential biomarker to predict cellular response to genotoxic treatments in MDS and to identify patients with defects in DNA repair. Such patients with worse prognosis may require a different therapeutic regimen to prevent progression to AML. These findings suggest levels may be used as a biological biomarker to determine the DNA repair capacity of hematopoietic stem cells from patients with MDS and as a clinical biomarker to inform decisions regarding patient selection for treatments that target DNA repair. http://cancerres.aacrjournals.org/content/canres/78/20/5767/F1.large.jpg .
| Item Type: | Article |
|---|---|
| Additional Information: | This article is available to all UHB staff and students login using a UHB Athens Account. Register for Athens here - https://openathens.nice.org.uk/ |
| Subjects: | QW Microbiology. Immunology QZ Pathology. Oncology WH Haemic and lymphatic systems. Haematology |
| Divisions: | Planned IP Care > Oncology and Clinical Haematology |
| Related URLs: | |
| Depositing User: | Beth Connors |
| Date Deposited: | 11 Oct 2019 14:18 |
| Last Modified: | 05 May 2022 07:24 |
| URI: | http://www.repository.uhblibrary.co.uk/id/eprint/2470 |
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