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Fig. 7 | Journal of Experimental & Clinical Cancer Research

Fig. 7

From: Differences between intrinsic and acquired nucleoside analogue resistance in acute myeloid leukaemia cells

Fig. 7

SAMHD1 and DCK regulate CNDAC cross-resistance of AML cell lines adapted to drugs from different classes. (A) Representative Western blots of SAMHD1, phosphorylated SAMHD1 (pSAMH1), DGK, and DCK in HL-60 sublines adapted to cytarabine (Ara-C), arabinosylguanine (Ara-G), 5-azacytidine (AZA), fludarabine (FLU), 6-mercaptopurine (6-MP), venetoclax (VENE), olaparib (OLA), and volasertib (VOLA). GAPDH served as loading control. (B) CNDAC concentrations that reduce cell viability by 50% (IC50s) in drug-adapted HL-60 sublines. Horizontal lines and error bars represent means ± SD of three independent experiments, each performed in three technical replicates. p-values were determined by two-tailed Student’s t-tests (*p < 0.05; **p < 0.01; ***p < 0.001). (C) Correlation of CNDAC IC50 values with cellular SAMHD1 or DCK protein levels, quantified using the near-infrared Western blot image shown in (A) to determine the ratio SAMHD1/GAPDH or DCK/GAPDH. (D) CNDAC dose-response curves in drug-adapted HL-60 sublines in the absence or presence of VPX virus-like particles (VPX-VLPs, cause SAMHD1 depletion) or VPR virus-like particles (VPR-VLPs, negative control). Each symbol represents the mean ± SD of three technical replicates of one representative experiment out of three. Concentrations that reduce AML cell viability by 50% (IC50s) ± SD and Western Blots showing SAMHD1 degradation by VPXVLPs are provided. (E) CNDAC or cytarabine (Ara-C) dose-response curve in cytarabineadapted MV4-11 or MOLM-13 cells (characterised by loss of DCK expression) stably transduced with either DCK (pWPI+DCK) or an empty vector (pWPI) in the absence or presence of VPX virus-like particles (VPX-VLPs), or VPR virus-like particles (VPR-VLPs). Each symbol represents the mean ± SD of three technical replicates of one representative experiment out of three. IC50s (mean ± SD) and Western Blots showing successful transduction with DCK and SAMHD1 degradation by VPX-VLPs are provided

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