Literature search services are currently unavailable. During our hosting provider's UPS upgrade we experienced a hardware failure and are currently working to resolve the issue.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Ddx18 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) of DDX18 in acute myeloid leukemia (AML) patient samples. RNA encoding wild-type DDX18 and 3 NSVs rescued the hematopoietic defect, indicating normal DDX18 activity. RNA encoding one mutation, DDX18-E76del, was unable to rescue hematopoiesis, and resulted in reduced myeloid cell numbers in ddx18(hi1727/+) embryos, indicating this NSV likely functions as a dominant-negative allele. These studies demonstrate the use of the zebrafish as a robust in vivo system for assessing the function of genes mutated in AML, which will become increasingly important as more sequence variants are identified by next-generation resequencing technologies.

Pubmed ID: 21653321


  • Payne EM
  • Bolli N
  • Rhodes J
  • Abdel-Wahab OI
  • Levine R
  • Hedvat CV
  • Stone R
  • Khanna-Gupta A
  • Sun H
  • Kanki JP
  • Gazda HT
  • Beggs AH
  • Cotter FE
  • Look AT



Publication Data

July 28, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: 5T32 CA009382-26

Mesh Terms

  • Alleles
  • Animals
  • Blotting, Western
  • Cell Cycle
  • Cell Separation
  • DEAD-box RNA Helicases
  • Embryo, Nonmammalian
  • Flow Cytometry
  • Hematopoiesis
  • Hematopoietic Stem Cells
  • Humans
  • In Situ Hybridization
  • Leukemia, Myeloid, Acute
  • Mutagenesis, Site-Directed
  • Mutation
  • Myeloid Cells
  • Polymerase Chain Reaction
  • Zebrafish
  • Zebrafish Proteins