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

被引：0
作者：
H J M de Jonge
C M Woolthuis
A Z Vos
A Mulder
E van den Berg
P M Kluin
K van der Weide
E S J M de Bont
G Huls
E Vellenga
J J Schuringa
机构：
[1] University Medical Center Groningen,Department of Experimental Hematology and Department of Pediatrics, Division of Pediatric Oncology/Hematology
[2] University of Groningen,Department of Experimental Hematology
[3] University Medical Center Groningen,Department of Clinical Chemistry
[4] University of Groningen,Department of Genetics
[5] University Medical Center Groningen,Department of Pathology and Medical Biology
[6] University of Groningen,Department of Pediatrics, Division of Pediatric Oncology/Hematology
[7] University Medical Center Groningen,undefined
[8] University of Groningen,undefined
[9] University Medical Center Groningen,undefined
[10] University of Groningen,undefined
[11] University Medical Center Groningen,undefined
[12] University of Groningen,undefined
来源：
Leukemia | 2011年 / 25卷
关键词：
Acute myeloid leukemia; gene expression profiling; leukemic stem cells; prognostic factors; CD34; cells; transcriptome analysis;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
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页码：1825 / 1833
页数：8
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