Del(5q) promotes genome instability. (A) Hematopoietic differentiation (%CD45⁺) of isogenic TP53 R209fs (TP53^+/−) and TP53 R209fs;del(5q) iPSCs; mean ± standard error of the mean. Two iPSCs per genotype, 2 experiments. **P = .003, t test. (B) Colony-forming potential of TP53 R209fs (TP53^+/−) and TP53 R209fs;del(5q) CD34⁺5F HPCs. Full dataset is shown in supplemental Figure 6A. Left: undifferentiated CFU (+Dox). Middle: differentiated CFU (–Dox). Right: representative erythroid (BFU-E) and myeloid (CFU-GM) colonies. Two iPSCs per genotype, 2 experiments. **P = .001, t test. (C) Chromosomal location of downregulated genes (P < .1; 1.5-fold) in del(5q) HPCs. RNA sequencing was performed on TP53 R209fs (TP53^+/−) and TP53 R209fs;del(5q) CD34⁺5F cells; t test, 2 iPSCs, 2 experiments. (D) Top downregulated GO categories in TP53;del(5q) CD34-5F cells. Left: GO categories ranked by -log of FWER P value. Right: gene set enrichment of GO Chromosome segregation and Chromosome instability gene sets³⁵  in TP53^+/− vs TP53;del(5q). Top del(5q) CIN/DDR genes listed. (E) DNA double-strand breaks measured by γ-H2AX foci in CD34⁺5F cells 30 minutes and 5 hours after 4 Gy irradiation. Median ± 95% CI, >100 cells, 2 experiments. ***P < .0001, Mann-Whitney U test. (F) Loss of TP53 heterozygosity detected by 17q FISH in CD34-5F cells cultured for 1 month after 4 Gy of γ-irradiation. CC17, control probe.