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Turkmen S.,Institute For Medizinische Genetik | Riehn M.,Institute For Medizinische Genetik | Klopocki E.,Institute For Medizinische Genetik | Molkentin M.,Medizinische Klinik fur Hamatologie | And 2 more authors.
Genes Chromosomes and Cancer | Year: 2011

Abnormalities of the long arm of chromosome 6 are a common feature in various B-cell malignancies. In most cases, the genes involved have not yet been clearly identified. We have molecularly characterized the recently established Burkitt lymphoma cell line BLUE-1 that carries a t(6;20)(q15;q11.2) rearrangement in addition to the typical t(8;14) with MYC-IGH fusion. To identify the gene loci involved on both chromosomes we applied a sequential BAC clone mapping strategy. By using RT-PCR we were finally able to detect a chimeric mRNA transcript showing a fusion of the first (non-coding) exon of BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2) on 6q15 to the second exon of BCL2L1 (BCL-X) on 20q11. Various fusion transcripts were detected for different BCL2L1 (BCL-XL) isoforms. The fusion ultimately results in strong expression of the BCL2L1 (BCL-XL) anti-apoptosis protein, as demonstrated by immunoblotting. This is the first report that shows the involvement of both BCL2L1 and the transcription factor BACH2 in a chromosomal rearrangement. It points to BACH2 as a possibly important target in lymphomas with 6q aberrations, although other genes on 6q are probably also involved in these cases. Moreover, it suggests that members of the BCL2 anti-apoptosis gene family other than BCL2 itself might also be involved in lymphoma. © 2011 Wiley-Liss, Inc.


Gansauer A.,University of Bonn | Okkel A.,University of Bonn | Schwach L.,University of Bonn | Wagner L.,Medizinische Klinik fur Hamatologie | And 2 more authors.
Beilstein Journal of Organic Chemistry | Year: 2014

An operationally simple, convenient, and mild strategy for the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute 'second-generation' functionalized titanocene building blocks for further synthetic elaboration. Our synthesis is modular and large numbers of the complexes can in principle be prepared in short periods of time. Some of the triazole-substituted titanocenes display high cyctotoxic activity against BJAB cells. Comparison of the most active complexes allows the identification of structural features essential for biological activity. © 2014 Gansäuer et al; licensee Beilstein-Institut.


PubMed | Medizinische Klinik fur Hamatologie, University of Bonn and Abteilung fur Kinderonkologie hamatologie Kinderkrankenhaus der Stadt Cologne Amsterdamerstrasse 59
Type: | Journal: Beilstein journal of organic chemistry | Year: 2014

An operationally simple, convenient, and mild strategy for the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute second-generation functionalized titanocene building blocks for further synthetic elaboration. Our synthesis is modular and large numbers of the complexes can in principle be prepared in short periods of time. Some of the triazole-substituted titanocenes display high cyctotoxic activity against BJAB cells. Comparison of the most active complexes allows the identification of structural features essential for biological activity.

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