Molecular-genetic insights in pediatric T-cell acute lymphoblastic leukemia

T-ALL is an aggressive T-cell malignancy with an inferior treatment outcome compared to B-lineage ALL. Intensive T-ALL research efforts during the last years lead to the identification of multiple genetic abnormalities that cooperate in the malignant transformation of thymocytes. Currently and in contrast to B-lineage ALL, genetic abnormalities are clinically not used for therapy stratification. Further progress on the treatment of T-ALL will require further genetic characterization, which will provide us with a better understanding of the pathogenesis of T-ALL and hopefully will lead to improved treatment schedules. As the general scope of this thesis, we performed genome-wide copy number analysis using array-CGH for the identification of novel genomic rearrangements in T-ALL that possibly relate to treatment outcome, i.e. prognostic factors, or provide further insight in the pathogenesis of T-cell leukemia

LMO2 (LIM domain only 2 (rhombotin-like 1))

Review on LMO2 (LIM domain only 2 (rhombotin-like 1)), with data on DNA, on the protein encoded, and where the gene is implicated

del(11)(p12p13)

Review on del(11)(p12p13), with data on clinics, and the genes involved

Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust Study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 mu g/kg/wk) and weight. based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91(41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice. (Ada gastroenterol. belg., 2010, 73, 5-11)

ParMap, an algorithm for the identification of small genomic insertions and deletions in nextgen sequencing data

<p>Abstract</p> <p>Background</p> <p>Next-generation sequencing produces high-throughput data, albeit with greater error and shorter reads than traditional Sanger sequencing methods. This complicates the detection of genomic variations, especially, small insertions and deletions.</p> <p>Findings</p> <p>Here we describe ParMap, a statistical algorithm for the identification of complex genetic variants, such as small insertion and deletions, using partially mapped reads in nextgen sequencing data.</p> <p>Conclusions</p> <p>We report ParMap's successful application to the mutation analysis of chromosome X exome-captured leukemia DNA samples.</p

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Effectiveness and tolerability of pegylated interferon alfa2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 μg/kg/wk) and weight-based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91 (41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community- based clinical practice

Bioink properties before, during and after 3D bioprinting

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction