Transcriptional upregulation of p21/WAF/Cip1 in myeloid leukemic blasts expressing AML1-ETO

Haematologica. 2008 Nov;93(11):1728-33. doi: 10.3324/haematol.13044. Epub 2008 Sep 11.


An inducible model for conditional expression of AML1-ETO in myeloid U-937 cells was generated previously to determine cellular effects of AML1-ETO and to identify target genes. Induction of AML1-ETO expression in U-937 resulted in reduced cell growth, G1 arrest and apoptosis. Microarray analysis showed more genes up-regulated than down-regulated (180 vs. 69). Clustering of AML1-ETO-positive and -negative cell lines was possible based on these differentially expressed genes. p21/WAF/Cip1 (CDKN1A) was up-regulated 4.6-fold upon induction of AML1-ETO which was confirmed in additional experiments. Knock-down of AML1-ETO by siRNA could reduce p21/WAF/Cip1 expression in Kasumi-1 cells. mRNA expression analysis of p21/WAF/Cip1 in a large cohort of acute myeloid leukemia patients demonstrated a significantly higher expression in AML1-ETO-positive leukemia. The increased expression of p21/WAF/Cip1 in primary leukemic blasts suggests that elevated p21/WAF/Cip1 levels may contribute to specific features observed in AML1-ETO positive leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blast Crisis / genetics*
  • Blast Crisis / pathology
  • Blotting, Northern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 21
  • Chromosomes, Human, Pair 8
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • DNA-Binding Proteins / genetics*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Genes, p53
  • Humans
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / pathology
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins / genetics*
  • RUNX1 Translocation Partner 1 Protein
  • Transcription Factors / genetics*
  • Transcription, Genetic*
  • Translocation, Genetic
  • Up-Regulation
  • rho GTP-Binding Proteins / genetics*


  • CDKN1A protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1 protein, human
  • RUNX1T1 protein, human
  • Transcription Factors
  • rho GTP-Binding Proteins