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- Buitenkamp, Trudy D., et al.
(author)
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Acute lymphoblastic leukemia in children with Down syndrome : a retrospective analysis from the Ponte di Legno study group
- 2014
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:1, s. 70-77
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Journal article (peer-reviewed)abstract
- Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- < 1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 x 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups.
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- Roels, Juliette, et al.
(author)
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Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia
- 2020
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In: Blood cancer discovery. - : American Association for Cancer Research. - 2643-3249. ; 1:3, s. 274-289
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Journal article (peer-reviewed)abstract
- Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.
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- Vassal, Gilles, et al.
(author)
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Challenges for Children and Adolescents With Cancer in Europe: The SIOP-Europe Agenda
- 2014
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 61:9, s. 1551-1557
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Journal article (peer-reviewed)abstract
- In Europe, 6,000 young people die of cancer yearly, the commonest disease causing death beyond the age of 1 year. In addition, 300,000-500,000 European citizens are survivors of a childhood cancer and up to 30% of them have severe long-term sequelae of their treatment. Increasing both cure and quality of cure are the two goals of the European paediatric haematology/oncology community. SIOPE coordinates and facilitates research, care and training which are implemented by the 18 European study groups and 23 national paediatric haematology/oncology societies. SIOPE is the European branch of the International Society of Paediatric Oncology and one of the six founding members of the European Cancer Organisation. SIOPE is preparing its strategic agenda to assure long-term sustainability of clinical and translational research in paediatric malignancies over the next 15 years. SIOPE tackles the issues of equal access to standard care and research across Europe and improvement of long term follow up. SIOPE defined a comprehensive syllabus for training European specialists. A strong partnership with parent, patient and survivor organisations is being developed to successfully achieve the goals of this patient-centred agenda. SIOPE is advocating in the field of EU policies, such as the Clinical Trials Regulation and the Paediatric Medicine Regulation, to warrant that the voice of young people is heard and their needs adequately addressed. SIOPE and the European community are entirely committed to the global agenda against childhood cancers to overcome the challenges to increasing both cure and quality of cure of young people with cancer. (c) 2014 Wiley-Liss, Inc., A Wiley Company. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.
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- Wcisło, Balbina, et al.
(author)
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Numerical analysis of ellipticity condition for large strain plasticity
- 2018
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In: Computer Methods in Mechanics, CMM 2017 : Proceedings of the 22nd International Conference on Computer Methods in Mechanics - Proceedings of the 22nd International Conference on Computer Methods in Mechanics. - : Author(s). - 9780735416147 ; 1922
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Conference paper (peer-reviewed)abstract
- This paper deals with the numerical investigation of ellipticity of the boundary value problem for isothermal finite strain elasto-plasticity. Ellipticity can be lost when softening occurs. A discontinuity surface then appears in the considered material body and this is associated with the ill-posedness of the boundary value problem. In the paper the condition for ellipticity loss is derived using the deformation gradient and the first Piola-Kirchhoff stress tensor. Next, the obtained condition is implemented and numerically tested within symbolic-numerical tools AceGen and AceFEM using the benchmark of an elongated rectangular plate with imperfection in plane stress and plane strain conditions.
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