Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 7072
© 2008 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lannert, H. Articles by Ho, A. D. Search for Related Content PubMed Articles by Lannert, H. Articles by Ho, A. D.

Abstract

Expression of S100 proteins in normal human hematopoietic stem cells and in AML

Medical Clinic of the University Heidelberg, Heidelberg, Germany; EMBL, Heidelberg, Germany

7072

Background: In the quest to reduce mortality and morbidity from cancer, there is continued effort to identify novel biomarkers to aid in the early detection and the accurate prediction of tumour behaviour. One group of proteins that is emerging as a potentially important group of markers in multiple tumour types is the S100 family of calcium-binding proteins. There is increasing evidence that altered expression of S100 family members is seen in many cancers including breast, lung, bladder, kidney, thyroid, gastric, prostate and oral cancers. S100 proteins are commonly up-regulated in tumours and this is often associated with tumour progression. We focused our expression- investigations on different subsets of highly enriched CD34+ stem cells from different human origins: cord blood (CB), bone marrow (BM), as well as CD34+ leukemia cells (AML M2), thus e.g. to identify new protein targets for leukemia therapy. Methods: Mononuclear cells were isolated by a standard Ficoll-Hypaque gradient separation method from the different blood sources. An Auto-MACS (Miltenyi) and FACS Vantage SE cell sorter (Becton Dickinson) was used to highly enrich (>99%) CD34+ cells fractions. Sample preparation: Total RNA was isolated from sorted 1 x 10e6 cells by standard methods using RNA isolation kit (Qiagen). For gene expression analysis topic-defined PIQOR^TM stem cell microarrays (936 genes) were performed. The quantitative proteinexpression was analyzed by western blotting. The subcellular localizations of the identified proteins were performed by fluorescence and confocal microscopy of all cell fractions. Results: 1. Significant mRNA overexpression of S100A10 and S100A11 in microarray analysis correlates directly to the protein overexpression in AML. 2. There was a translocation of S100A11 expression from exclusively nuclear in human stem cells to cytoplasmic and nuclear in AML cells. Conclusions: S100A10 and S100A11 are overexpressed in AML. In addition, S100A11 undergoes a nucleocytoplasmic translocation which may have a direct influence on the proliferation of the AML cells. S100A10 and S100A11 have been suggested to have potential roles in carcinogenesis and tumour progression but their expression has not been described before in human hematopoietic stem cells and AML cells.

No significant financial relationships to disclose.

Abstract presentation from the 2008 ASCO Annual Meeting