Chapuy, Björn

[["dc.bibliographiccitation.firstpage","1576"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Leukemia"],["dc.bibliographiccitation.lastpage","1586"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Chapuy, Björn"],["dc.contributor.author","Koch, R."],["dc.contributor.author","Radunski, Ulf"],["dc.contributor.author","Corsham, Sabrina"],["dc.contributor.author","Cheong, Naeun"],["dc.contributor.author","Inagaki, Nobuya"],["dc.contributor.author","Ban, N."],["dc.contributor.author","Wenzel, D."],["dc.contributor.author","Reinhardt, D."],["dc.contributor.author","Zapf, Antonia"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Kosari, F."],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Wulf, Gerald G."],["dc.date.accessioned","2018-11-07T11:12:37Z"],["dc.date.available","2018-11-07T11:12:37Z"],["dc.date.issued","2008"],["dc.description.abstract","Multidrug resistance (MDR) seriously limits the efficacy of chemotherapy in patients with cancer and leukemia. Active transport across membranes is essential for such cellular drug resistance, largely provided by ATP-binding cassette (ABC) transport proteins. Intracellular drug sequestration contributes to MDR; however, a genuine intracellular ABC transport protein with MDR function has not yet been identified. Analyzing the intrinsic drug efflux capacity of leukemic stem cells, we found the ABC transporter A3 (ABCA3) to be expressed consistently in acute myeloid leukemia (AML) samples. Greater expression of ABCA3 is associated with unfavorable treatment outcome, and in vitro, elevated expression induces resistance toward a broad spectrum of cytostatic agents. ABCA3 remains localized within the limiting membranes of lysosomes and multivesicular bodies, in which cytostatics are efficiently sequestered. In addition to AML, we also detected ABCA3 in a panel of lymphohematopoietic tissues and transformed cell lines. In conclusion, we identified subcellular drug sequestration mediated by the genuinely intracellular ABCA3 as being a clinically relevant mechanism of intrinsic MDR."],["dc.identifier.doi","10.1038/leu.2008.103"],["dc.identifier.isi","000258413400013"],["dc.identifier.pmid","18463677"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6063"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53706"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0887-6924"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Intracellular ABC transporter A3 confers multidrug resistance in leukemia cells by lysosomal drug sequestration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1528"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","HAEMATOLOGICA-THE HEMATOLOGY JOURNAL"],["dc.bibliographiccitation.lastpage","1536"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Chapuy, Björn"],["dc.contributor.author","Panse, Melanie"],["dc.contributor.author","Radunski, Ulf"],["dc.contributor.author","Koch, Raphael"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","lnagaki, Nobuya"],["dc.contributor.author","Haase, Detlef"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Wulf, Gerald G."],["dc.date.accessioned","2018-11-07T11:22:41Z"],["dc.date.available","2018-11-07T11:22:41Z"],["dc.date.issued","2009"],["dc.description.abstract","Background Inhibition of BCR-ABL tyrosine kinase activity has evolved as a mainstay of therapy for patients with chronic myeloid leukemia. However, a fraction of leukemic cells persists under targeted therapy and can lead to disease progression on cessation of treatment. Design and Methods We analyzed bone marrow progenitor cells with the side population phenotype, and characterized the role of the intracellular ABC transporter A3 in imatinib detoxification. Results BCR-ABL-positive leukemic cells contribute to the side population cell compartment in untreated patients. Such leukemic side population cells, as well as CD34-positive progenitors from chronic myeloid leukemia samples, strongly express the intracellular ABCA3. Functionally, ABCA3 levels are critical for the susceptibility of chronic myeloid leukemia blast cell lines to specific BCR-A-BL inhibition by imatinib. The transporter is localized in the limiting membrane of lysosomes and multivesicular bodies, and intracellular [(14)C]-labeled imatinib accumulates in such organelles. The lysosomal storage capacity increases with ABCA3 expression, thus regulating imatinib sequestration. Conclusions The intracellular ABC transporter A3 is expressed in chronic myeloid leukemia progenitor cells and may contribute to intrinsic imatinib resistance by facilitating lysosomal sequestration in chronic myeloid leukemia cells."],["dc.identifier.doi","10.3324/haematol.2009.008631"],["dc.identifier.isi","000272165800009"],["dc.identifier.pmid","19880777"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5958"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56030"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0390-6078"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]