%0 Journal Article %1 Kronenwett2005 %A Kronenwett, Ralf %A Butterweck, Ulf %A Steidl, Ulrich %A Kliszewski, Slawomir %A Neumann, Frank %A Bork, Simone %A Blanco, Elena Diaz %A Roes, Nicole %A Gräf, Thorsten %A Brors, Benedikt %A Eils, Roland %A Maercker, Christian %A Kobbe, Guido %A Gattermann, Norbert %A Haas, Rainer %D 2005 %J Oncogene %K Adult; Aged; Analysis; Antigens, Array BCR-ABL CD34, Cells, Chain Chronic, Cytometry; Down-Regulation; Expression Flow G-Protein-Coupled, Gene Hematopoietic Humans; Leukemia, Middle Myelogenous, Neoplastic; Oligonucleotide Phenotype; Polymerase Positive, Profiling; Reaction; Receptors, Regulation, Reverse Sequence Stem Transcriptase Up-Regulation analysis; biosynthesis; genetics/immunology; physiology; %N 34 %P 5313--5324 %R 10.1038/sj.onc.1208596 %T Distinct molecular phenotype of malignant CD34(+) hematopoietic stem and progenitor cells in chronic myelogenous leukemia. %U http://dx.doi.org/10.1038/sj.onc.1208596 %V 24 %X Chronic myelogenous leukemia (CML) is a malignant disorder of the hematopoietic stem cell characterized by the BCR-ABL oncogene. We examined gene expression profiles of highly enriched CD34(+) hematopoietic stem and progenitor cells from patients with CML in chronic phase using cDNA arrays covering 1.185 genes. Comparing CML CD34(+) cells with normal CD34(+) cells, we found 158 genes which were significantly differentially expressed. Gene expression patterns reflected BCR-ABL-induced functional alterations such as increased cell-cycle and proteasome activity. Detoxification enzymes and DNA repair proteins were downregulated in CML CD34(+) cells, which might contribute to genetic instability. Decreased expression of junction plakoglobulin and CXC chemokine receptor 4 (CXCR-4) might facilitate the release of immature precursors from bone marrow in CML. GATA-2 was upregulated in CML CD34(+) cells, suggesting an increased self-renewal in comparison with normal CD34(+) cells. Moreover, we found upregulation of the proto-oncogene SKI and of receptors for neuromediators such as opioid mu1 receptor, GABA B receptor, adenosine A1 receptor, orexin 1 and 2 receptors and corticotropine-releasing hormone receptor. Treatment of CML progenitor cells with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) resulted in a dose-dependent significant inhibition of clonogenic growth by 40\% at a concentration of 10(-5) M, which could be reversed by the equimolar addition of the receptor agonist 2-chloro-N6-cyclopentyladenosine (P<0.05). The incubation of normal progenitor cells with DPCPX resulted in an inhibition of clonogenic growth to a significantly lesser extent in comparison with CML cells (P<0.05), suggesting that the adenosine A1 receptor is of functional relevance in CML hematopoietic progenitor cells.

@article{Kronenwett2005, __markedentry = {[bbrors:6]}, abstract = {Chronic myelogenous leukemia (CML) is a malignant disorder of the hematopoietic stem cell characterized by the BCR-ABL oncogene. We examined gene expression profiles of highly enriched CD34(+) hematopoietic stem and progenitor cells from patients with CML in chronic phase using cDNA arrays covering 1.185 genes. Comparing CML CD34(+) cells with normal CD34(+) cells, we found 158 genes which were significantly differentially expressed. Gene expression patterns reflected BCR-ABL-induced functional alterations such as increased cell-cycle and proteasome activity. Detoxification enzymes and DNA repair proteins were downregulated in CML CD34(+) cells, which might contribute to genetic instability. Decreased expression of junction plakoglobulin and CXC chemokine receptor 4 (CXCR-4) might facilitate the release of immature precursors from bone marrow in CML. GATA-2 was upregulated in CML CD34(+) cells, suggesting an increased self-renewal in comparison with normal CD34(+) cells. Moreover, we found upregulation of the proto-oncogene SKI and of receptors for neuromediators such as opioid mu1 receptor, GABA B receptor, adenosine A1 receptor, orexin 1 and 2 receptors and corticotropine-releasing hormone receptor. Treatment of CML progenitor cells with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) resulted in a dose-dependent significant inhibition of clonogenic growth by 40\% at a concentration of 10(-5) M, which could be reversed by the equimolar addition of the receptor agonist 2-chloro-N6-cyclopentyladenosine (P<0.05). The incubation of normal progenitor cells with DPCPX resulted in an inhibition of clonogenic growth to a significantly lesser extent in comparison with CML cells (P<0.05), suggesting that the adenosine A1 receptor is of functional relevance in CML hematopoietic progenitor cells.}, added-at = {2015-04-09T12:36:21.000+0200}, author = {Kronenwett, Ralf and Butterweck, Ulf and Steidl, Ulrich and Kliszewski, Slawomir and Neumann, Frank and Bork, Simone and Blanco, Elena Diaz and Roes, Nicole and Gr{\"{a}}f, Thorsten and Brors, Benedikt and Eils, Roland and Maercker, Christian and Kobbe, Guido and Gattermann, Norbert and Haas, Rainer}, biburl = {https://www.bibsonomy.org/bibtex/29eb318e945a22f817715493e3ec40188/bbrors}, doi = {10.1038/sj.onc.1208596}, institution = {Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany. kronenwett@med.uni-duesseldorf.de}, interhash = {3b0635862b0fd7f0fee2dd7f9009174b}, intrahash = {9eb318e945a22f817715493e3ec40188}, journal = {Oncogene}, keywords = {Adult; Aged; Analysis; Antigens, Array BCR-ABL CD34, Cells, Chain Chronic, Cytometry; Down-Regulation; Expression Flow G-Protein-Coupled, Gene Hematopoietic Humans; Leukemia, Middle Myelogenous, Neoplastic; Oligonucleotide Phenotype; Polymerase Positive, Profiling; Reaction; Receptors, Regulation, Reverse Sequence Stem Transcriptase Up-Regulation analysis; biosynthesis; genetics/immunology; physiology;}, language = {eng}, medline-pst = {ppublish}, month = Aug, number = 34, owner = {bbrors}, pages = {5313--5324}, pii = {1208596}, pmid = {15806158}, timestamp = {2015-04-09T12:36:21.000+0200}, title = {Distinct molecular phenotype of malignant CD34(+) hematopoietic stem and progenitor cells in chronic myelogenous leukemia.}, url = {http://dx.doi.org/10.1038/sj.onc.1208596}, volume = 24, year = 2005 }