Disease progression impairs hematopoietic differentiation. Hematopoietic differentiation (day 14) of isogenic MDS-RA1 patient iPSCs showing representative flow plots (A) and percentage of CD45⁺ hematopoietic cells for each genotype (B): normal (ISO), t(4;12), t(4;12);SF3B1 (t;SF3B1), t(4;12);SF3B1;EZH2 (t;S;EZH2), and t(4;12);SF3B1;EZH2;del(5q) (t;S;E;del5q). (B) Mean ± standard deviation (SD) of 2 to 3 iPSCs per genotype, 4 independent experiments. (C) Percentage of EdU-positive actively cycling CD34⁺CD45⁺ isogenic HPCs after 3 hours of EdU labeling. (D) Percentage of annexin V⁺ apoptotic CD34⁺CD45⁺ HPCs. (C-D) Mean ± SD of 1 iPSC line per genotype, 3 independent experiments. (E) Hematopoietic differentiation efficiency (%CD45⁺ cells) of normal (ISO) and t(4;12);SF3B1;EZH2 (MDS) iPSCs generated by using Sendai reprogramming. SF3B1 p.G742D-ablated (p.G740fs, NM_012433.2: c.2219delG) labeled “-G742D,” and noncorrected SF3B1-mutant iPSCs, were generated by using CRISPR/Cas9. Quantitation is shown as mean ± SD of 2 independent iPSCs, 2 to 3 independent experiments. For all panels, ***P < .001, **P < .005, *P < .05; unpaired t test vs normal isogenic iPSCs unless indicated. ns, not significant.