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Cells 2019, 8(2), 103; https://doi.org/10.3390/cells8020103

Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma

1,2,3,4,5,6,†
,
6,7,8,9,10,11,†
,
6,12
and
12,*
1
INSERM U1218, Université de Bordeaux, 33076 Bordeaux, France
2
INSERM U1138, 75006 Paris, France
3
Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France
4
Université Pierre et Marie Curie, Sorbonne Université, 75006 Paris, France
5
Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France
6
TRANSAUTOPHAGY: European Network for Multidisciplinary Research and Translation of Autophagy Knowledge, COST Action CA15138
7
INSERM, UMR1037 CRCT, F-31000 Toulouse, France
8
Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France
9
CNRS, ERL5294 CRCT, F-31000 Toulouse, France
10
Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA
11
European Research Initiative on ALK-related malignancies (ERIA), F-31000 Toulouse, France
12
Institute of Pathology, Division of Experimental Pathology, University of Bern, Murtenstrasse 31, CH-3008 Bern, Switzerland
*
Author to whom correspondence should be addressed.
These two authors contributed equally.
Received: 31 December 2018 / Revised: 26 January 2019 / Accepted: 28 January 2019 / Published: 30 January 2019
(This article belongs to the Special Issue Autophagy in Age-Related Human Diseases)
Full-Text   |   PDF [1641 KB, uploaded 4 February 2019]   |  

Abstract

Haematopoiesis is a tightly orchestrated process where a pool of hematopoietic stem and progenitor cells (HSPCs) with high self-renewal potential can give rise to both lymphoid and myeloid lineages. The HSPCs pool is reduced with ageing resulting in few HSPC clones maintaining haematopoiesis thereby reducing blood cell diversity, a phenomenon called clonal haematopoiesis. Clonal expansion of HSPCs carrying specific genetic mutations leads to increased risk for haematological malignancies. Therefore, it comes as no surprise that hematopoietic tumours develop in higher frequency in elderly people. Unfortunately, elderly patients with leukaemia or lymphoma still have an unsatisfactory prognosis compared to younger ones highlighting the need to develop more efficient therapies for this group of patients. Growing evidence indicates that macroautophagy (hereafter referred to as autophagy) is essential for health and longevity. This review is focusing on the role of autophagy in normal haematopoiesis as well as in leukaemia and lymphoma development. Attenuated autophagy may support early hematopoietic neoplasia whereas activation of autophagy in later stages of tumour development and in response to a variety of therapies rather triggers a pro-tumoral response. Novel insights into the role of autophagy in haematopoiesis will be discussed in light of designing new autophagy modulating therapies in hematopoietic cancers. View Full-Text
Keywords: macroautophagy; haematopoiesis; leukaemia; lymphomas; therapy response; ageing macroautophagy; haematopoiesis; leukaemia; lymphomas; therapy response; ageing
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Djavaheri-Mergny, M.; Giuriato, S.; Tschan, M.P.; Humbert, M. Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma. Cells 2019, 8, 103.

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