American Society of Hematology

Figure 7.

$Targeting ZDHHC21 is a potential therapeutic strategy for relapsed/refractory AML. (A-G) The in vivo effect of ZDHHC21 depletion on leukemogenesis in R/R PDX-AML xenograft model subjected to primary and secondary transplant. NSG mice underwent transplantation with shCtrl or shZDHHC21-transfected AML blasts. (A) Body weight of NSG mice. (B) The survival time of NSG mice. Data are presented as mean ± SD (n = 10). ∗∗∗P < .001 vs shCtrl. The significance analysis was conducted by log-rank test. (C) The population of hCD45+mCD45− leukemia cells in the peripheral blood of NSG mice. (D) Spleen weight of NSG mice on 39 days after transplantation (mean ±SD; n = 3). (E) The population of hCD45+mCD45− leukemia cells and CD34+ and CD11b+ cells in the spleen (SP) of NSG mice (mean± SD; n = 3). (F) The body weight of secondary transplant mice. (G) Kaplan-Meier survival curves of secondary transplant mice upon ZDHHC21 knockdown (n = 10). ∗∗∗P < .001 vs shCtrl. The significance analysis was conducted by log-rank test. (H) Mitochondrial OCR of HL60 cells after treatment with control, 2BP, Ara-C, or Ara-C + 2BP for 24 hours. OCR was assessed using a Seahorse analyzer. (I) The effect of 2BP, Ara-C, or Ara-C + 2BP on the proliferation of HL60 cells. HL60 cells were treated with drugs for 72 hours, followed by trypan blue exclusion test. (J) The effect of 2BP, Ara-C, or Ara-C + 2BP on the apoptosis of HL60 cells for 72 hours. The apoptosis was confirmed by PI/annexin V assay. Data are presented as mean ± SD (n = 3). n.s., P > .05; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 vs Ctrl. #P <.05; ##P < .01; ###P < .001 vs Ara-C. (K) The effect of Ara-C or Ara-C + 2BP on the apoptosis of primary AML blast cells and LSCs. Primary AML blast cells were directly separated from the bone marrow of patients using lymphocyte monocytes separation medium. LSCs were sorted by CD34 marker from AML specimens. The apoptosis rate of cells was detected after treatment with drug for 3 days. ∗∗P < .01; ∗∗∗P < .001. The significance analysis was conducted by a two-tailed unpaired t test or a one-way analysis of variance.$

Targeting ZDHHC21 is a potential therapeutic strategy for relapsed/refractory AML. (A-G) The in vivo effect of ZDHHC21 depletion on leukemogenesis in R/R PDX-AML xenograft model subjected to primary and secondary transplant. NSG mice underwent transplantation with shCtrl or shZDHHC21-transfected AML blasts. (A) Body weight of NSG mice. (B) The survival time of NSG mice. Data are presented as mean ± SD (n = 10). ∗∗∗P < .001 vs shCtrl. The significance analysis was conducted by log-rank test. (C) The population of hCD45⁺mCD45⁻ leukemia cells in the peripheral blood of NSG mice. (D) Spleen weight of NSG mice on 39 days after transplantation (mean ±SD; n = 3). (E) The population of hCD45⁺mCD45⁻ leukemia cells and CD34⁺ and CD11b⁺ cells in the spleen (SP) of NSG mice (mean± SD; n = 3). (F) The body weight of secondary transplant mice. (G) Kaplan-Meier survival curves of secondary transplant mice upon ZDHHC21 knockdown (n = 10). ∗∗∗P < .001 vs shCtrl. The significance analysis was conducted by log-rank test. (H) Mitochondrial OCR of HL60 cells after treatment with control, 2BP, Ara-C, or Ara-C + 2BP for 24 hours. OCR was assessed using a Seahorse analyzer. (I) The effect of 2BP, Ara-C, or Ara-C + 2BP on the proliferation of HL60 cells. HL60 cells were treated with drugs for 72 hours, followed by trypan blue exclusion test. (J) The effect of 2BP, Ara-C, or Ara-C + 2BP on the apoptosis of HL60 cells for 72 hours. The apoptosis was confirmed by PI/annexin V assay. Data are presented as mean ± SD (n = 3). n.s., P > .05; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 vs Ctrl. #P <.05; ##P < .01; ###P < .001 vs Ara-C. (K) The effect of Ara-C or Ara-C + 2BP on the apoptosis of primary AML blast cells and LSCs. Primary AML blast cells were directly separated from the bone marrow of patients using lymphocyte monocytes separation medium. LSCs were sorted by CD34 marker from AML specimens. The apoptosis rate of cells was detected after treatment with drug for 3 days. ∗∗P < .01; ∗∗∗P < .001. The significance analysis was conducted by a two-tailed unpaired t test or a one-way analysis of variance.

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