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Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients.(More)
Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating(More)
BACKGROUND Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined. METHODS We studied a cohort of 221 children with(More)
Freezing avoidance conferred by different types of antifreeze proteins in various polar and subpolar fishes represents a remarkable example of cold adaptation, but how these unique proteins arose is unknown. We have found that the antifreeze glycoproteins (AFGPs) of the predominant Antarctic fish taxon, the notothenioids, evolved from a pancreatic(More)
BACKGROUND About a fifth of children with acute T-lymphoblastic leukaemia (T-ALL) succumb to the disease, suggesting an unrecognised biological heterogeneity that might contribute to drug resistance. We postulated that T-ALL originating from early T-cell precursors (ETPs), a recently defined subset of thymocytes that retain stem-cell-like features, would(More)
BACKGROUND Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase(More)
Innate immune responses are triggered by the activation of pattern-recognition receptors (PRRs). The Arabidopsis PRR FLAGELLIN-SENSING 2 (FLS2) senses bacterial flagellin and initiates immune signaling through association with BAK1. The molecular mechanisms underlying the attenuation of FLS2 activation are largely unknown. We report that flagellin induces(More)
Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the(More)
After anterior interbody fusion in the lumbar spine, the accelerated degeneration of the disc adjacent to the fusion levels was clinically observed. To understand the stress distribution of the adjacent disc, this study created a finite element model of the lumbar spine from L1-L5 vertebral body. The fusion model modified from the intact model was used to(More)
MOTIVATION Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR). However, rigorous control of the FDR at a preselected level is often impractical. Consequently, it has been suggested to use the q-value as an estimate of the proportion of false discoveries among a set of(More)