Gene expression profiling in the leukemic stem cell-enriched CD34+ fraction identifies target genes that predict prognosis in normal karyotype AML

Leukemia. 2011 Dec;25(12):1825-33. doi: 10.1038/leu.2011.172. Epub 2011 Jul 15.


In order to identify acute myeloid leukemia (AML) CD34(+)-specific gene expression profiles, mononuclear cells from AML patients (n=46) were sorted into CD34(+) and CD34(-) subfractions, and genome-wide expression analysis was performed using Illumina BeadChip Arrays. AML CD34(+) and CD34(-) gene expression was compared with a large group of normal CD34(+) bone marrow (BM) cells (n=31). Unsupervised hierarchical clustering analysis showed that CD34(+) AML samples belonged to a distinct cluster compared with normal BM and that in 61% of the cases the AML CD34(+) transcriptome did not cluster together with the paired CD34(-) transcriptome. The top 50 of AML CD34(+)-specific genes was selected by comparing the AML CD34(+) transcriptome with the AML CD34(-) and CD34(+) normal BM transcriptomes. Interestingly, for three of these genes, that is, ankyrin repeat domain 28 (ANKRD28), guanine nucleotide binding protein, alpha 15 (GNA15) and UDP-glucose pyrophosphorylase 2 (UGP2), a high transcript level was associated with a significant poorer overall survival (OS) in two independent cohorts (n=163 and n=218) of normal karyotype AML. Importantly, the prognostic value of the continuous transcript levels of ANKRD28 (OS hazard ratio (HR): 1.32, P=0.008), GNA15 (OS HR: 1.22, P=0.033) and UGP2 (OS HR: 1.86, P=0.009) was shown to be independent from the well-known risk factors FLT3-ITD, NPM1c(+) and CEBPA mutation status.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / metabolism*
  • Biomarkers, Tumor / genetics*
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cells, Cultured
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Leukemic
  • Humans
  • Karyotyping
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Risk Factors
  • Young Adult


  • Antigens, CD34
  • Biomarkers, Tumor