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- Storlazzi, CT, et al.
(author)
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MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene
- 2006
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 15:6, s. 933-942
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Journal article (peer-reviewed)abstract
- Double minutes (dmin)-circular, extra-chromosomal amplifications of specific acentric DNA fragments-are relatively frequent in malignant disorders, particularly in solid tumors. In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), dmin are observed in similar to 1% of the cases. Most of them consist of an amplified segment from chromosome band 8q24, always including the MYC gene. Besides this information, little is known about their internal structure. We have characterized in detail the genomic organization of 32 AML and two MDS cases with MYC-containing dmin. The minimally amplified region was shown to be 4.26 Mb in size, harboring five known genes, with the proximal and the distal amplicon breakpoints clustering in two regions of similar to 500 and 600 kb, respectively. Interestingly, in 23 (68%) of the studied cases, the amplified region was deleted in one of the chromosome 8 homologs at 8q24, suggesting excision of a DNA segment from the original chromosomal location according to the 'episome model'. In one case, sequencing of both the dmin and del(8q) junctions was achieved and provided definitive evidence in favor of the episome model for the formation of dmin. Expression status of the TRIB1 and MYC genes, encompassed by the minimally amplified region, was assessed by northern blot analysis. The TRIB1 gene was found over-expressed in only a subset of the AML/MDS cases, whereas MYC, contrary to expectations, was always silent. The present study, therefore, strongly suggests that MYC is not the target gene of the 8q24 amplifications.
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| 2. |
- Hehlmann, Ruediger, et al.
(author)
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The European LeukemiaNet : achievements and perspectives
- 2011
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:1, s. 156-162
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Journal article (peer-reviewed)abstract
- The only way to cure leukemia is by cooperative research. To optimize research, the European Leukemia Net integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European Leukemia Net has steadily expanded and has unified leukemia research across Europe. The European Leukemia Net grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European Leukemia Net has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European Leukemia Net-Foundation) will take over when the support of the European Commission ends.
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| 3. |
- Saussele, S., et al.
(author)
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Klinische Forschung im „European LeukemiaNet”
- 2006
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In: Deutsche Medizinische Wochenschrift. - : Georg Thieme Verlag KG. - 0012-0472 .- 1439-4413. ; 131:43, s. 2423-2426
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Journal article (peer-reviewed)abstract
- Because of their mortality, morbidity and incidence in all age groups, leukemias represent a challenge and a cost factor for society. In research, they serve as models for a variety of diseases and have a pivotal function in basic research and for patient care. The European LeukemiaNet (ELN) is a EU funded Network of excellence. Its major goal is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among 78 national leukemia study groups and their 83 interdisciplinary partner groups that deal with the leukemias in research and in patient care in 22 countries. The network integrates about 1000 researchers in 125 participating institutions. In practice, cooperation between clinical and research groups is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation, and also increase information transfer from top research institutions to clinical translation. The improved cooperation and the accelerated information transfer from the „bench to the bedside” results in a better patient care that ultimately results in improved survival of patients and in superior competitiveness of involved research workers and clinicians. The major goals are: Establishing common information and communication structures, Creation of European networks for each leukemia Establishing European platforms for each inter-disciplinary speciality Performing clinical trials on an European level Establishing European leukemia registries Developing common definitions and standards Developing guidelines and meta-analyses Spread of excellence To reach these goals the network is organized in 17 Workpackages (WPs) each of which is subdivided into several components and deliverables. The WPs represent central services, set up European networks for each major leukemia or related syndrome and interdisciplinary European platforms for diagnostic specialities, and support treatment research, registries, meta-analyses and guidelines. After the second year of networking, the main structures concerning management, communication and information of the ELN have been established and consolidated. Web-based information is available on the central website (www.leukemia-net.org). Communication is accomplished through annual symposia, regular network and WP-meetings (nearly 60 in 2005), website, and the biannual newsletters. A central randomization service and registries are available for distinct leukemia entities, and a prototype of the electronic data capture facility service has been implemented. Several studies were initiated and are ongoing on a European level. Nearly all WPs have prepared or are preparing guidelines or consensus papers, e. g. guidelines on CML therapy, definitions for transplantation associated microangiopathy (TAM), therapy of infections in leukemias, harmonization of molecular monitoring in CML and a consensus on microarray-technology based diagnostics in leukemias. The main goals of the second funding period have been achieved, and thus the ELN is well prepared for further progress in its goals to improve diagnosis and treatment of the leukemias.
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