Targeting of PAK1 inhibits AML patient cells including immature, leukemia stem cell-enriched populations while sparing healthy stem and progenitor cells. (A) Colony formation assay of primary AML patient MNC samples or healthy control MNC samples treated with IPA-3 (healthy, n = 4; AML, n = 5) or FRAX-597 (healthy, n = 4; AML, n = 3). (B) Cell viability (DAPI⁻Annexin V⁻) of CD34⁺CD38⁻ cells from AML patients and healthy controls after 24 hours in vitro culture with IPA-3 or FRAX-597 (n = 3 for each drug). (C) Cell viability (DAPI⁻Annexin V⁻) of CD34⁺CD38⁺ cells from AML patients and healthy controls after 24 hours in vitro culture with IPA-3 or FRAX-597 (n = 3 for each drug). (D) Percentage bone marrow engraftment of human CD45⁺CD33⁺ cells 6 weeks following xenografting with primary AML patient samples treated with IPA-3. Experiment performed in duplicate with 2 independent primary AML patient samples. (E) Kaplan-Meier curve of overall survival of patients with high vs low PAK1 expression in CD34⁺ bone marrow cells isolated from MDS patients. Patients with high PAK1 expression are those with PAK1 expression levels higher than the median expression level of PAK1 in the dataset. The P value (log-rank test) is indicated. *P < .05 and **P < .01 for all experiments.