{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:46:42Z","timestamp":1781689602634,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T00:00:00Z","timestamp":1199664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Philadelphia (Ph) chromosome\u2010positive leukemia is characterized by the BCR\/ABL1 fusion protein that affects a wide range of signal transduction pathways. The knowledge about its downstream target genes is, however, still quite limited. To identify novel BCR\/ABL1\u2010regulated genes we used global gene expression profiling of several Ph\u2010positive and Ph\u2010negative cell lines treated with imatinib. Following imatinib treatment, the Ph\u2010positive cells showed decreased growth, viability, and reduced phosphorylation of BCR\/ABL1 and STAT5. In total, 142 genes were identified as being dependent on BCR\/ABL1\u2010mediated signaling, mainly including genes involved in signal transduction, e.g. the JAK\/STAT, MAPK, TGFB, and insulin signaling pathways, and in regulation of metabolism. Interestingly, BCR\/ABL1 was found to activate several genes involved in negative feedback regulation (<jats:italic>CISH<\/jats:italic>, <jats:italic>SOCS2<\/jats:italic>, <jats:italic>SOCS3<\/jats:italic>, <jats:italic>PIM1<\/jats:italic>, <jats:italic>DUSP6<\/jats:italic>, and <jats:italic>TNFAIP3<\/jats:italic>), which may act to indirectly suppress the tumor promoting effects exerted by BCR\/ABL1. In addition, several genes identified as deregulated upon <jats:italic>BCR\/ABL1<\/jats:italic> expression could be assigned to the TGFB and NFkB signaling pathways, as well as to reflect the metabolic adjustments needed for rapidly growing cells. Apart from providing important pathogenetic insights into <jats:italic>BCR\/ABL1<\/jats:italic>\u2010mediated leukemogenesis, the present study also provides a number of pathways\/individual genes that may provide attractive targets for future development of targeted therapies. This article contains Supplementary Material available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.interscience.wiley.com\/jpages\/1045-2257\/suppmat\">http:\/\/www.interscience.wiley.com\/jpages\/1045\u20132257\/suppmat<\/jats:ext-link>. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20528","type":"journal-article","created":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T22:46:46Z","timestamp":1199746006000},"page":"267-275","source":"Crossref","is-referenced-by-count":12,"title":["Gene expression analysis of BCR\/ABL1\u2010dependent transcriptional response reveals enrichment for genes involved in negative feedback 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