Format

Send to

Choose Destination
See comment in PubMed Commons below
Leukemia. 2011 Dec;25(12):1825-33. doi: 10.1038/leu.2011.172. Epub 2011 Jul 15.

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

Author information

  • 1Department of Experimental Hematology, Division of Pediatric Oncology/Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Abstract

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.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk