NUP98-fusion–protein-driven leukemia is highly sensitive to pharmacological CDK4/CDK6 inhibition. (A) Proliferation curves of murine NUP98/JARID1A-expressing leukemia cells in the presence of indicated concentrations of Palbociclib (mean ± SD; n = 3). (B) Colony formation assay of murine NUP98/JARID1A-expressing leukemia cells in the presence of dimethyl sulfoxide (DMSO) or Palbociclib. Colony numbers were normalized to DMSO (mean ± SD; n = 3). (C) Representative image of colonies in the presence of DMSO or Palbociclib after 3 rounds of replating, ×40 original magnification. (D) Flow cytometric analyses of Mac-1/Gr-1 surface marker expression in NUP98/JARID1A-expressing AML cells treated with indicated concentrations of Palbociclib (mean ± SD; n = 3). (E) Representative Cytospin images illustrating the morphology of NUP98/JARID1A-expressing AML cells 7 days after DMSO or Palbociclib treatment, ×400 original magnification. (F) Flow cytometric analyses of AnnexinV expression in NUP98/JARID1A-expressing leukemia cells treated with indicated concentrations of Palbociclib (mean ± SD; n = 3). (G-H) Dose-response curves of Palbociclib-mediated growth inhibition of murine leukemia cells (G) and primary patient cells (H) driven by different fusion proteins (mean ± standard error of the mean; n = 3). (I) Kaplan-Meier survival curves with statistical analysis using the log-rank test of C57BL/6 Ly5.1 recipients transplanted with murine NUP98/NSD1-driven leukemia cells after vehicle or Palbociclib treatment (50 mg/kg; n = 4). (J) Kaplan-Meier survival curves with statistical analysis using the log-rank test of NSG mice transplanted with NUP98/NSD1-PDX AML cells after vehicle or Palbociclib treatment (50 mg/kg; n = 4). *P < .05, **P < .01, ***P < .001, ****P < .0001.