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. 2019 Sep;104(9):e393-e397.
doi: 10.3324/haematol.2018.206821. Epub 2019 Feb 28.

Adult patients with de novo acute myeloid leukemia show a functional deregulation of redox balance at diagnosis which is correlated with molecular subtypes and overall survival

Julie Mondet  1   2 , Caroline Lo Presti  2   3 , Catherine Garrel  4 , Kristina Skaare  5 , Clara Mariette  6 , Sylvain Carras  7 , Sophie Park  2   6 , Martin Carré  6 , Claude-Eric Bulabois  6 , Lysiane Molina  6 , Rémy Gressin  6 , Anne Thiebaut  6 , Stéphane Courby  6 , Nuria Socoro-Yuste  8 , Patrice Faure  4 , Anne Mc Leer-Florin  9   2 , Jean-Yves Cahn  2   6 , Pascal Mossuz  10   3
Affiliations

Adult patients with de novo acute myeloid leukemia show a functional deregulation of redox balance at diagnosis which is correlated with molecular subtypes and overall survival

Julie Mondet et al. Haematologica. 2019 Sep.
No abstract available

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Figures

Figure 1.
Figure 1.
Reactive oxygen species profiles and antioxidant markers of leukemic cells. (A) Schema of reactive oxygen species (ROS) modulators stimulating or inhibiting NADPH oxidase and mitochondria used in the ex vivo ROS assays. (B) ROS profiles showing the effects of different ROS modulators in blast cells from bone marrow. Statistical analysis: Wilcoxon test for paired samples. (C) Spider chart of ROS profiles according to leukemic abnormalities. Colored lines represent leukemic abnormalities. Note that ROS profiles from t(8;21), inv(16) patients showed more variability in ROS production after the addition of modulators. “Others” refers to acute myeloid leukemia (AML) that did not express any of the listed abnormalities. (D) Distribution of erythrocytic superoxide dismutase activity at diagnosis in healthy donors (HD) and AML patients according to genetic abnormalities. (E) Distribution of erythrocytic glutathione peroxidase activity in HD and AML patients according to genetic abnormalities. (F) Distribution of oxidized glutathione in HD and AML patients according to genetic abnormalities. (B, D, E, F) *P<0.05, **P<0.01. PMA: phorbol 12-myristate 13-acetate; DPI: diphenyleneiodonium; AMA: antimycin A; Rot: rotenone; NOX: NADPH oxidase; SOD: superoxide dismutase; GPX; glutathione peroxidase.
Figure 2.
Figure 2.
Reactive oxygen species profiles of non-leukemic cells from healthy donors and patients with acute myeloid leukemia. (A) At baseline, levels of reactive oxygen species (ROS) in neutrophils from patients with acute myeloid leukemia (AML) were higher than those in neutrophils from healthy donors. However, neutrophils from AML patients were less reactive to phorbol 12-myristate 13-acetate stimulation. In contrast, in lymphocytes (B) and monocytes (C) from AML patients. ROS production was lower whatever the ROS conditions.**P<0.01. HD: healthy donors; PMA: phorbol 12-myristate 13-acetate; DPI: diphenyleneiodonium; AMA: antimycin A; Rot: rotenone.
Figure 3.
Figure 3.
Prognostic value of antioxidant markers and leukemic reactive oxygen species profiles. (A) Forest plot representing the risk of death (with hazard ratios and 95% confidence intervals) according to antioxidant markers and malondialdehyde levels. (B) Kaplan-Meier survival curves of patients with acute myeloid leukemia (AML) receiving chemotherapy according to the cut-off for reduced/oxidative glutathione ratio (< vs. ≥81.5). (C) Kaplan-Meier survival curves of AML patients receiving chemotherapy according to the cut-off for thiol levels (< or ≥349 μmol/L). (D) Forest plot representing the risk of death (with hazard ratios and 95% confidence intervals) according to reactive oxygen species (ROS) production by leukemic cells from bone marrow exposed to different ROS modulators (log-transformed variables). (E) Kaplan-Meier survival curves of AML patients receiving chemotherapy according to the cut-off for mean fluorescence intensity (MFI) in response to ROS modulators (< vs. ≥5,500). High levels of MFI were predictive of survival (P=0.004). MV: multivariate analysis; UV: univariate analysis; MDA: malondialdehyde; SOD: superoxide dismutase; GPX: glutathione peroxidase; AMA: antimycin A; Rot: rotenone; PMA: phorbol 12-myristate 13-acetate; DPI: diphenyleneiodonium.
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