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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4210-4218. Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-01-0103. This Article Full Text (PDF) All Versions of this Article: 2004-01-0103v1 104/13/4210    most recent 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 Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, G. Articles by Young, N. S Search for Related Content PubMed PubMed Citation Articles by Chen, G. Articles by Young, N. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 21, 2004 Accepted July 26, 2004 Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities Guibin Chen, Weihua Zeng, Akira Miyazato, Eric Billings, Jaroslaw P Maciejewski, Sachiko Kajigaya, Elaine M Sloand, and Neal S Young* Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: youngn{at}nhlbi.nih.gov. Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndrome (MDS). Chromosomal abnormalities in general predict prognosis, and patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization with RNA from pooled patient samples, and a small sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these two techniques. Microarray data were confirmed by gene amplification and flow cytometric measurement of expression of specific genes using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. Additionally, there were distinctive gene expression patterns that distinguished the two karotypes. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory response (such as TGF- and TGF-receptor), signal transduction (IGF, IGFR1, MYD118, and Rad51), and cell-cycle control (CCNE1 and CDK2), and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis (HOX9A, BRCA2, and PLAB) and apoptosis (TRAIL and TRAIL-DR5), and down-regulation of genes controlling cell growth and differentiation (SPHAR, p21, MAP, and GATA). These results imply distinct molecular mechanisms for monosomy 7 or trisomy 8 MDS and implicate specific pathogeneic pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. K. Ahn, H.-S. Cha, E.-M. Koh, S.-H. Kim, Y. G. Kim, C.-K. Lee, and B. Yoo Behcet's disease associated with bone marrow failure in Korean patients: clinical characteristics and the association of intestinal ulceration and trisomy 8 Rheumatology, August 1, 2008; 47(8): 1228 - 1230. [Abstract] [Full Text] [PDF] L. Nilsson, P. Eden, E. Olsson, R. Mansson, I. Astrand-Grundstrom, B. Strombeck, K. Theilgaard-Monch, K. Anderson, R. Hast, E. Hellstrom-Lindberg, et al. The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes Blood, October 15, 2007; 110(8): 3005 - 3014. [Abstract] [Full Text] [PDF] E. M. Sloand, L. Pfannes, G. Chen, S. Shah, E. E. Solomou, J. Barrett, and N. S. Young CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins Blood, March 15, 2007; 109(6): 2399 - 2405. [Abstract] [Full Text] [PDF] W. Yuan, J. E. Payton, M. S. Holt, D. C. Link, M. A. Watson, J. F. DiPersio, and T. J. Ley Commonly dysregulated genes in murine APL cells Blood, February 1, 2007; 109(3): 961 - 970. [Abstract] [Full Text] [PDF] A. Ganser, M. A. Morgan, and E. M. Weissinger Going from genes to proteins in myelodysplastic syndromes PNAS, January 23, 2007; 104(4): 1109 - 1110. [Full Text] [PDF] E. M. Sloand, A. S. M. Yong, S. Ramkissoon, E. Solomou, T. C. Bruno, S. Kim, M. Fuhrer, S. Kajigaya, A. J. Barrett, and N. S. Young Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor PNAS, September 26, 2006; 103(39): 14483 - 14488. [Abstract] [Full Text] [PDF] W. Zeng, A. Miyazato, G. Chen, S. Kajigaya, N. S. Young, and J. P. Maciejewski Interferon-{gamma}-induced gene expression in CD34 cells: identification of pathologic cytokine-specific signature profiles Blood, January 1, 2006; 107(1): 167 - 175. [Abstract] [Full Text] [PDF] A. Sternberg, S. Killick, T. Littlewood, C. Hatton, A. Peniket, T. Seidl, S. Soneji, J. Leach, D. Bowen, C. Chapman, et al. Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome Blood, November 1, 2005; 106(9): 2982 - 2991. [Abstract] [Full Text] [PDF]

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