Human leukemia is sensitive to ALDH3A2 depletion. (A) ALDH3A2 expression in pretreatment AML patients with normal karyotype from the Meltezer database.32 (B) Overall survival in patients with high vs low ALDH3A2 expression. Data were divided into ALDH3A2-high and ALDH3A2-low patients around the median of the distribution of ALDH3A2 expression. (C) Relative ALDH3A2 expression in human AML cell lines. (D) Effective knockdown of ALDH3A2 expression in THP1 cells with 2 independent shRNAs (ALDH3A2-sh-A and ALDH3A2-sh-B) compared with control shRNA. (E) ALDH3A2 knockdown by 2 independent shRNAs decreased cell growth in 5 different AML cell lines as compared with cells infected with control shRNA. (F) ALDH3A2 knockdown by 1 or 2 independent shRNAs (depending on number of patient cells available) decreased the growth of 3 different primary AML samples as compared with cells infected with control shRNA. Data are representative of ≥2 independent experiments; n = 3 replicates per cell line per experiment. Data are represented as mean ± standard deviation. P > .05 was considered nonsignificant. *P < .05, **P < .01, ***P < .001, ****P < .0001. GAPDH, glyceraldehyde-3-phosphate dehydrogenase.