Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep;102(9):e344-e347.
doi: 10.3324/haematol.2017.166389. Epub 2017 May 26.

Acute myeloid leukemia stem cell function is preserved in the absence of autophagy

Amy H Porter  1 , Lucie Leveque-El Mouttie  1 , Therese Vu  1   2 , Claudia Bruedigam  1 , Joanne Sutton  1 , Sebastien Jacquelin  1 , Geoffrey R Hill  1   2   3 , Kelli P A MacDonald  1 , Steven W Lane  4   2   3
Affiliations

Acute myeloid leukemia stem cell function is preserved in the absence of autophagy

Amy H Porter et al. Haematologica. 2017 Sep.
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Autophagy is activated during leukemic transformation. Loss of autophagic flux causes a reduction in clonality and delays leukemia onset VavCre;Atg7fl/fl MLL-AF9. (A) Western blot comparison of Atg7 and LC3-I and LC3-II expression levels in primary bone marrow (BM) cells isolated from MLL-AF9 and wild-type (WT) mice (n=4). (B) Colony forming assay of WT and VavCre;Atg7fl/fl models of MLL-AF9 represented as number of colonies per input of cells (%) represented as median (n=7–8). (C) Representative flow cytometry plots from in vitro cells using Annexin V and Sytox. (D) Early and (E) late stage apoptosis (n=3–4) of WT, LysmCre:Atg7fl/fl and VavCre; Atg7fl/fl models of MLL-AF9. (F) Kaplan-Meier survival curve of recipient mice injected with MLL-AF9-GFP transduced BM (input 8×105 cells/mouse, n=8–9 recipients). (G) Leukemia burden of transplanted mice represented as the number of GFP+ white blood cells in the peripheral blood 6 or 8 weeks after transplantation (n=7–10). (H) The spleen weight harvested from primary recipients at acute myeloid leukemia (AML) onset (n=3–8). (I) Protein expression levels of Atg7, LC3-I and LC3-II isolated from MLL-AF9 spleen cells after in vivo transplantation in mice (n=4). (J) Quantification of the percentage of γH2AX+ cells in the G0/G1 stage of the cell cycle via flow cytometry (n=5–6). (K) Analysis of the percentage of LSCs in each stage of the cell cycle using flow cytometry (n=5–6). All data are mean plus individual dots represent biological replicates. Statistical significance calculated using non-parametric Kruskal Wallis one-way analysis of variance with Dunn’s correction for multiple testing corrections (Prism v.7.0, Graphpad).
Figure 2.
Figure 2.
Autophagy is not required for leukemia stem cell (LSC) function. (A) Survival of mice injected with 1×105 acute myeloid leukemia (AML) cells derived from primary, transplanted mice (n=7–8). (B) Leukemia burden of transplanted mice represented as the number of GFP+ white blood cells in the peripheral blood at week 2 (n=5) and (C) week 3 after transplantation (n=7–8). (D) The spleen weight and bone marrow (BM) cellularity (two femur and tibia) of mice at end point analysis (n=7–8). (E) Survival analysis of secondary transplantation of 5×105 BCR-ABL/NUP98-HOXA9 transduced cells harvested from primary recipients (n=4–5). (F) The percentage of GFP+ cells and white blood cells (WBC) in the peripheral blood of BCR-ABL/NUP98-HOXA9 secondary recipients. (G) The frequency of LSCs in the BM of mice injected with primary MLL-AF9 at time of disease onset (n=7). (H) Relative expression levels of alternative autophagy genes by quantitative real-time PCR (n=6–7) and (I) Western blot n=3. Data represent two independent experiments with pooled data. Each experiment produced similar results. Statistical significance calculated using non-parametric Kruskal Wallis one-way analysis of variance with Dunn’s correction for multiple comparisons, except where noted.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Auberger P, Puissant A. Autophagy, a key mechanism of oncogenesis and resistance in leukemia. Blood. 2016;129(5):547–552. - PubMed
    1. Mortensen M, Soilleux EJ, Djordjevic G, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011;208(3):455–467. - PMC - PubMed
    1. Mortensen M, Ferguson DJ, Edelmann M, et al. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci USA. 2010;107(2):832–837. - PMC - PubMed
    1. Xu X, Araki K, Li S, et al. Autophagy is essential for effector CD8(+) T cell survival and memory formation. Nat Immunol. 2014;15(12):1152–1161. - PMC - PubMed
    1. Le Texier L, Lineburg KE, Cao B, et al. Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease. JCI Insight. 2016;1(15):e86850. - PMC - PubMed

Publication types

Substances

  NODES
Note 1
twitter 2