Journal
AUTOPHAGY
Volume 7, Issue 9, Pages 1069-1070Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.7.9.15886
Keywords
acute myeloid leukemia; autophagy; myeloproliferation; hematopoietic stem cells; mitophagy; reactive oxygen species; hematopoietic progenitors; Atg7; hematopoietic malignancy
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Funding
- Biotechnology and Biological Sciences Research Council [BB/G021422/1] Funding Source: Medline
- BBSRC [BB/G021422/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/G021422/1] Funding Source: researchfish
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The regulated lysosomal degradation pathway of autophagy prevents cellular damage and thus protects from malignant transformation. Autophagy is also required for the maturation of various hematopoietic lineages, namely the erythroid and lymphoid ones, yet its role in adult hematopoietic stem cells (HSCs) remained unexplored. While normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs or early progenitors leads to leukemia. Mechanisms protecting HSCs from cellular damage are therefore essential to prevent hematopoietic malignancies. By conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system, we found that autophagy is required for the maintenance of true HSCs and therefore also of downstream hematopoietic progenitors. Loss of autophagy in HSCs leads to the expansion of a progenitor cell population in the bone marrow, giving rise to a severe, invasive myeloproliferation, which strongly resembles human acute myeloid leukemia (AML).
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