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Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion(More)
NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases;(More)
Dramatic advances in next generation sequencing technologies have provided a novel opportunity to understand the molecular genetics of chronic lymphocytic leukemia through the comprehensive detection of genetic lesions. While progress is being made in elucidating the clinical significance of recurrently mutated genes, layers of complexity have been added to(More)
PURPOSE Immunoglobulin G-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires. EXPERIMENTAL DESIGN Using purpose-built(More)
We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic(More)
Single-cell transcriptome analysis overcomes problems inherently associated with averaging gene expression measurements in bulk analysis. However, single-cell analysis is currently challenging in terms of cost, throughput and robustness. Here, we present a method enabling massive microarray-based barcoding of expression patterns in single cells, termed(More)
PURPOSE Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. EXPERIMENTAL DESIGN We conducted a large-scale subcloning study of the IG rearrangements of(More)
PURPOSE The role of antigen(s) in shaping the T-cell repertoire in chronic lymphocytic leukemia, although relevant for understanding malignant cell interactions with cognate T cells, is largely unexplored. EXPERIMENTAL DESIGN Here we profiled the T-cell receptor β chain gene repertoire in 58 chronic lymphocytic leukemia patients, focusing on cases(More)
Pr ecis: This study suggests a route through which senescence can be defeated to blunt a fail-safe mechanism that can restrain the powerful oncogenic effects of deregulated MYC, which underpins the malignant development of most human tumors. Pr ecis: These findings encourage further evaluation of an innate immune regulator as a noninvasive biomarker that(More)