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CD147 as potential therapeutic target in AML
(Figure 6B). However, AC-73 induces autophagy by increasing the LC3-II/LC3-I ratio in leukemic blasts, as compared to control (-) leukemic cells, even at 2.5 or 5 mM (Figure 6C). However, combination of low-dose AC-73 (2.5 mM) and ATO or Ara-C (0.1 and 1 mM) more efficient- ly decreased leukemic blast viability, compared with sin- gle AC-73, ATO or Ara treatment (Figure 6D). Overall, our data indicate that AC-73 activates a non-apoptotic autophagic form of cell death in AML blasts and increases the sensitivity of these cells to Ara-C or ATO agents.
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Analysis of CD147 expression in acute myeloid leukemia based on TCGA dataset
By providing selected genetic and clinical data from 200 AML patients, useful for prognosis and diagnosis, the TCGA dataset offered a unique opportunity to explore a possible relationship between the recurrent gene muta- tions observed in AML and the level of CD147 expres- sion. TCGA data set analysis indicates that CD147 level is particularly elevated in AML-M3, those AML subtypes bearing PML-RARA fusion gene1,26 (Figure 7A, RARA), in
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Figure 6. AC-73 decreases the survival of CD147+ acute myeloid leukemia (AML) cells exposed to chemotherapeutic agents and activates autophagy in AML cells.
(A) CD147 is expressed in the subfraction of CD34+CD371+ positive AML leukemic cells. (B) Dose response analysis of AC-73 treatment on leukemic cell apoptosis of AML-M2, AML-M3 and AML M5 blasts obtained from 5 AML (4, 5, 7, 8 and 10) patients, as compared to respective control (C) leukemic blasts; flow cytometry analysis of total apoptosis by Annexin V/ PI (%) is shown. (C) Western blot analysis of the autophagic-related LC3 marker shows its conversion from the LC3-I to LC3-II form in leukemic blasts treated in vitro with growing concentration of AC-73 as compared to control leukemic blasts (-). (D) Cell viability assays were performed on M2, M3 and M5 leukemic blasts, obtained from 5 AML patients (4), (5), (7), (8) and (10), and treated in vitro by AC-73 (2.5 mM) in combination with ATO or Ara-C (0.1 and 1 mM), as compared to control (C) leukemic blasts and to single treatment with AC-73, ATO and Ara-C. (A) One representative experiment is shown. (B and D) Mean±Standard Error of Mean of three independent experiments is shown. *P<0.05; **P<0.01; ***P<0.001; ns: not significant. (C) One representative western blot experiment out of three is shown. Actin was used as an internal control.
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