biostudies-literaturePayne EMNCI NIH HHS903-15https://www.ebi.ac.uk/biostudies/studies/S-EPMC3148170biostudies-literatureUnknown118(4)In a zebrafish mutagenesis screen to identify genes essential for myelopoiesis, we identified an insertional allele hi1727, which disrupts the gene encoding RNA helicase dead-box 18 (Ddx18). Homozygous Ddx18 mutant embryos exhibit a profound loss of myeloid and erythroid cells along with cardiovascular abnormalities and reduced size. These mutants also display prominent apoptosis and a G1 cell-cycle arrest. Loss of p53, but not Bcl-xl overexpression, rescues myeloid cells to normal levels, suggesting that the hematopoietic defect is because of p53-dependent G1 cell-cycle arrest. We then sequenced primary samples from 262 patients with myeloid malignancies because genes essential for myelopoiesis are often mutated in human leukemias. We identified 4 nonsynonymous sequence variants (NSVs) ofBloodDdx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML.PMC3148170R01 CA093152T32 CA0093825T32 CA009382-26Rhodes JBolli NGazda HTLook ATAbdel-Wahab OIKanki JPLevine RStone RBeggs AHCotter FEPayne EMHedvat CVKhanna-Gupta ASun HfalseDdx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML.In a zebrafish mutagenesis screen to identify genes essential for myelopoiesis, we identified an insertional allele hi1727, which disrupts the gene encoding RNA helicase dead-box 18 (Ddx18). Homozygous Ddx18 mutant embryos exhibit a profound loss of myeloid and erythroid cells along with cardiovascular abnormalities and reduced size. These mutants also display prominent apoptosis and a G1 cell-cycle arrest. Loss of p53, but not Bcl-xl overexpression, rescues myeloid cells to normal levels, suggesting that the hematopoietic defect is because of p53-dependent G1 cell-cycle arrest. We then sequenced primary samples from 262 patients with myeloid malignancies because genes essential for myelopoiesis are often mutated in human leukemias. We identified 4 nonsynonymous sequence variants (NSVs) of2011-01-01T00:00:00Z2011 Jul2026-04-18T11:15:05.778Z2025-07-13T03:04:46.49ZS-EPMC31481702165332110.1182/blood-2010-11-318022