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Perturbed hematopoiesis in mice lacking ATMIN

Anjos-Afonso, F; Loizou, JI; Bradburn, A; Kanu, N; Purewal, S; Da Costa, C; Bonnet, D; (2016) Perturbed hematopoiesis in mice lacking ATMIN. Blood , 128 (16) pp. 2017-2021. 10.1182/blood-2015-09-672980. Green open access

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Abstract

The ataxia telangiectasia mutated (ATM)-interacting protein ATMIN mediates noncanonical ATM signaling in response to oxidative and replicative stress conditions. Like ATM, ATMIN can function as a tumor suppressor in the hematopoietic system: deletion of Atmin under the control of CD19-Cre results in B-cell lymphomas in aging mice. ATM signaling is essential for lymphopoiesis and hematopoietic stem cell (HSC) function; however, little is known about the role of ATMIN in hematopoiesis. We thus sought to investigate whether the absence of ATMIN would affect primitive hematopoietic cells in an ATM-dependent or -independent manner. Apart from its role in B-cell development, we show that ATMIN has an ATM-independent function in the common myeloid progenitors (CMPs) by deletion of Atmin in the entire hematopoietic system using Vav-Cre. Despite the lack of lymphoma formation, ATMIN-deficient mice developed chronic leukopenia as a result of high levels of apoptosis in B cells and CMPs and induced a compensatory mechanism in which HSCs displayed enhanced cycling. Consequently, ATMIN-deficient HSCs showed impaired regeneration ability with the induction of the DNA oxidative stress response, especially when aged. ATMIN, therefore, has multiple roles in different cell types, and its absence results in perturbed hematopoiesis, especially during stress conditions and aging.

Type: Article
Title: Perturbed hematopoiesis in mice lacking ATMIN
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood-2015-09-672980
Publisher version: https://doi.org/10.1182/blood-2015-09-672980
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Aging, Animals, Apoptosis, Ataxia Telangiectasia Mutated Proteins, B-Lymphocytes, Chronic Disease, Gene Deletion, Hematopoiesis, Hematopoietic Stem Cells, Leukopenia, Mice, Mice, Knockout, Oxidative Stress, Transcription Factors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10026400
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