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

Fractal-like Distributions over the Rational Numbers in High-throughput Biological and Clinical Data

Recent developments in extracting and processing biological and clinical data are allowing quantitative approaches to studying living systems. High-throughput sequencing, expression profiles, proteomics, and electronic health records are some examples of such technologies. Extracting meaningful information from those technologies requires careful analysis of the large volumes of data they produce. In this note, we present a set of distributions that commonly appear in the analysis of such data. These distributions present some interesting features: they are discontinuous in the rational numbers, but continuous in the irrational numbers, and possess a certain self-similar (fractal-like) structure. The first set of examples which we present here are drawn from a high-throughput sequencing experiment. Here, the self-similar distributions appear as part of the evaluation of the error rate of the sequencing technology and the identification of tumorogenic genomic alterations. The other examples are obtained from risk factor evaluation and analysis of relative disease prevalence and co-mordbidity as these appear in electronic clinical data. The distributions are also relevant to identification of subclonal populations in tumors and the study of the evolution of infectious diseases, and more precisely the study of quasi-species and intrahost diversity of viral populations

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)

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

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