Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations
| Autor: | William G. Nelson, Meltem Gürel, Richard J. Jones, Jessica L. Gucwa, Milada S. Vala, Michael C. Haffner, Jonathan M. Gerber, Srinivasan Yegnasubramanian, David M. Esopi |
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| Rok vydání: | 2013 |
| Předmět: |
DNA Repair
Cellular differentiation HSC myeloid progenitor cells Transcriptome GAS2 0302 clinical medicine Transforming Growth Factor beta hemic and lymphatic diseases LSC Tumor Cells Cultured Cyclin D1 CML Chemokine CCL2 0303 health sciences Stem Cells Myeloid leukemia Cell Differentiation Research Papers leukemic stem cell Up-Regulation 3. Good health Leukemia Oncology 030220 oncology & carcinogenesis Neoplastic Stem Cells Stem cell Signal Transduction ALDH Down-Regulation DPP4 Biology 03 medical and health sciences chronic myeloid leukemia normal hematopoietic stem cell Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Progenitor cell CD25 CD26 Cell Proliferation 030304 developmental biology IL2RA Gene Expression Profiling Bone Morphogenetic Protein Receptors Transforming growth factor beta medicine.disease Cancer research biology.protein CD34 Kinase binding CD38 |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The persistence leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) despite tyrosine kinase inhibition (TKI) may explain relapse after TKI withdrawal. Here we performed genome-wide transcriptome analysis of highly refined CML and normal stem and progenitor cell populations to identify novel targets for the eradication of CML LSCs using exon microarrays. We identified 97 genes that were differentially expressed in CML versus normal stem and progenitor cells. These included cell surface genes significantly upregulated in CML LSCs: DPP4 (CD26), IL2RA (CD25), PTPRD, CACNA1D, IL1RAP, SLC4A4, and KCNK5. Further analyses of the LSCs revealed dysregulation of normal cellular processes, evidenced by alternative splicing of genes in key cancer signaling pathways such as p53 signaling (e.g. PERP, CDKN1A), kinase binding (e.g. DUSP12, MARCKS), and cell proliferation (MYCN, TIMELESS); downregulation of pro-differentiation and TGF-β/BMP signaling pathways; upregulation of oxidative metabolism and DNA repair pathways; and activation of inflammatory cytokines, including CCL2, and multiple oncogenes (e.g., CCND1). These data represent an important resource for understanding the molecular changes in CML LSCs, which may be exploited to develop novel therapies for eradication these cells and achieve cure. |
| Databáze: | OpenAIRE |
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