Figure 3.
ZDHHC21 regulates the stemness potential of LSCs and chemotherapy resistance. (A) Left: quantitative analysis of ZDHHC21 messenger RNA expression in patients with AML with (n = 34) or without (n = 105) MRD. Right: quantitative analysis of ZDHHC21 messenger RNA expression in patients with AML with low-risk stage (n = 72), standard-risk stage (n = 92), and high-risk stage (n = 12). Data are derived from the TARGET database. (B) Expression of ZDHHC21 in pre- and postchemotherapy flow-sorted AML blast populations (n =  6). The data are derived from the GSE162542 cohort. (C) Expression of ZDHHC21 in low LSC17 score and high LSC17 score from the TARGET database. (D) Expression of ZDHHC21 in different genetic subtypes of human AMLs. Data are derived from the TCGA database. (E) The correlation of ZDHHC21 protein expression with FLT3-ITD mutation in patients with AML. (F) Top: the protein levels of ZDHHC21 were measured by western blotting to evaluate the silencing efficiency of ZDHHC21 in HSCs or LSCs. HSCs from 2 healthy sources were used as controls. LSCs were sorted by CD34 marker from AML specimens. Bottom: cellular ATP levels of shZDHHC21-transfected HSCs or LSCs. ATP levels were normalized to their protein concentrations. LSC1 were sorted from patient AML28 via the CD34 marker, LSC2 were sorted from AML45, LSC3 were sorted from AML46, and LSC4 were sorted from AML33. (G) The relative proliferation of HSCs or LSCs infected with lentivirus-shZDHHC21. (H) The effect of shZDHHC21 on the colony-forming ability of HSCs and LSCs after culturing in methylcellulose medium for 2 weeks. (I) The inhibitory effect of 2BP on ATP production in HSCs and LSCs. Cells were treated with 2BP at a series of concentrations (0, 20, 40, 60 μM). (J) The relative proliferation of HSCs or LSCs treated with 2BP by a series of concentrations (0, 20, 40, 60 μM). (K) The effect of 2BP on the colony-forming ability of HSCs and LSCs after culturing in methylcellulose medium for 2 weeks. (L) Drug sensitivity analysis of primary patient cells. Primary AML cells were treated with chemotherapy drugs. The CellTiter-Glo measurement was used to determine the number of viable cells. Data are presented as mean ± SD (n = 3). n.s., P > .05; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. The significance analysis was conducted by a two-tailed unpaired t test or a one-way analysis of variance. MRD, minimal residual disease.

ZDHHC21 regulates the stemness potential of LSCs and chemotherapy resistance. (A) Left: quantitative analysis of ZDHHC21 messenger RNA expression in patients with AML with (n = 34) or without (n = 105) MRD. Right: quantitative analysis of ZDHHC21 messenger RNA expression in patients with AML with low-risk stage (n = 72), standard-risk stage (n = 92), and high-risk stage (n = 12). Data are derived from the TARGET database. (B) Expression of ZDHHC21 in pre- and postchemotherapy flow-sorted AML blast populations (n =  6). The data are derived from the GSE162542 cohort. (C) Expression of ZDHHC21 in low LSC17 score and high LSC17 score from the TARGET database. (D) Expression of ZDHHC21 in different genetic subtypes of human AMLs. Data are derived from the TCGA database. (E) The correlation of ZDHHC21 protein expression with FLT3-ITD mutation in patients with AML. (F) Top: the protein levels of ZDHHC21 were measured by western blotting to evaluate the silencing efficiency of ZDHHC21 in HSCs or LSCs. HSCs from 2 healthy sources were used as controls. LSCs were sorted by CD34 marker from AML specimens. Bottom: cellular ATP levels of shZDHHC21-transfected HSCs or LSCs. ATP levels were normalized to their protein concentrations. LSC1 were sorted from patient AML28 via the CD34 marker, LSC2 were sorted from AML45, LSC3 were sorted from AML46, and LSC4 were sorted from AML33. (G) The relative proliferation of HSCs or LSCs infected with lentivirus-shZDHHC21. (H) The effect of shZDHHC21 on the colony-forming ability of HSCs and LSCs after culturing in methylcellulose medium for 2 weeks. (I) The inhibitory effect of 2BP on ATP production in HSCs and LSCs. Cells were treated with 2BP at a series of concentrations (0, 20, 40, 60 μM). (J) The relative proliferation of HSCs or LSCs treated with 2BP by a series of concentrations (0, 20, 40, 60 μM). (K) The effect of 2BP on the colony-forming ability of HSCs and LSCs after culturing in methylcellulose medium for 2 weeks. (L) Drug sensitivity analysis of primary patient cells. Primary AML cells were treated with chemotherapy drugs. The CellTiter-Glo measurement was used to determine the number of viable cells. Data are presented as mean ± SD (n = 3). n.s., P > .05; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. The significance analysis was conducted by a two-tailed unpaired t test or a one-way analysis of variance. MRD, minimal residual disease.

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