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

de Jonge, H. J. M., Woolthuis, C. M., Vos, A. Z., Mulder, A., van den Berg, E., Kluin, P. M., van der Weide, K., de Bont, E. S. J. M., Huls, G., Vellenga, E. & Schuringa, J. J., Dec-2011, In : Leukemia. 25, 12, p. 1825-1833 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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. Leukemia (2011) 25, 1825-1833; doi:10.1038/leu.2011.172; published online 15 July 2011

Original languageEnglish
Pages (from-to)1825-1833
Number of pages9
JournalLeukemia
Volume25
Issue number12
Publication statusPublished - Dec-2011

    Keywords

  • Acute myeloid leukemia, gene expression profiling, leukemic stem cells, prognostic factors, CD34(+) cells, transcriptome analysis, ACUTE MYELOID-LEUKEMIA, ABILITY IN-VITRO, INTERNAL TANDEM DUPLICATION, ACUTE MYELOGENOUS LEUKEMIA, CYTOPLASMIC NUCLEOPHOSMIN, CYTOGENETIC ABNORMALITIES, FLT3 GENE, GROUP-B, VIVO, HEMATOPOIESIS

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