Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling.

The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that probably account for the various survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high-resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity is common in MCL and targets regions that are frequently affected by deletions.

Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior.

Background: The concept of "accelerated" chronic lymphocytic leukemia is frequently used by both pathologists and clinicians. However, neither histological criteria to define this form of chronic lymphocytic leukemia nor its clinical correlates and prognostic impact have been formally defined in large series of patients.

Design And Methods: Tissue biopsies from 100 patients with chronic lymphocytic leukemia were analyzed for the size of proliferation centers and their proliferation rate as assessed by mitosis count and Ki-67 immunostaining.

International network of cancer genome projects.

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Effects of the nonvolatile matrix on the aroma perception of wine.

Eighteen reconstituted wine samples were prepared by mixing nonvolatile and volatile fractions obtained from six different wines, two whites and four reds, with different characteristics, in an approach that makes it possible to have the same aroma composition in different nonvolatile matrices and vice versa. The aroma elicited by those reconstituted samples was described by a specifically trained sensory panel. Additional gas chromatography-olfactometric and gas chromatography-mass spectrometric studies were carried out to measure differences in aroma release.

Do we need to do fluorescence in situ hybridization analysis in myelodysplastic syndromes as often as we do?

Although conventional cytogenetics is considered the gold standard to detect chromosomal abnormalities in myelodysplastic syndromes (MDS), fluorescence in situ hybridization (FISH) is being increasingly used additionally. However, the real contribution of FISH analysis in the cytogenetic diagnosis of MDS has not been well defined. The aim of this study was to evaluate whether FISH studies are able to reveal chromosomal abnormalities in MDS patients undetected by conventional cytogenetics.

Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.

Background: Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score.

Methods: Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome.

Incidence and prognostic impact of secondary cytogenetic aberrations in a series of 145 patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with an aggressive behavior, characterized by the t(11;14)(q13;q32). Several secondary genetic abnormalities with a potential role in the oncogenic process have been described. Studies of large MCL series using conventional cytogenetics, and correlating with proliferation and survival, are scarce.

Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is typically a very aggressive disease with poor outcomes, but some cases display an indolent behavior that might not necessitate treatment at diagnosis. To define molecular criteria that might permit recognition of such cases, we compared the clinicopathologic features, gene expression, and genomic profile of patients who had indolent or conventional disease (iMCL or cMCL). Patients with iMCL displayed nonnodal leukemic disease with predominantly hypermutated IGVH and noncomplex karyotypes.

Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk.

To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio (OR) = 1.

Focus ion beam micromachined glass pipettes for cell microinjection.

Cell handling is currently hindered by rudimentary-manufactured manipulators. Restrictive designs of glass pipettes and other micromanipulators limit functionality and often damage cells, ultimately resulting in lysis. We present a novel technique to design and mill conventional glass pipettes at specifically chosen angles and geometries.

Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma.

A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL.

SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype.

Background: Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma.

Suitability of chloroplast LSU rDNA and its diverse group I introns for species recognition and phylogenetic analyses of lichen-forming Trebouxia algae.

To date, species identification of lichen photobionts has been performed principally on the basis of microscopic examinations and molecular data from nuclear-encoded genes. In plants, the chloroplast genome has been more readily exploited than the nuclear genome for systematic investigations. At the present time, very little information is available about the chloroplast genome of lichen-forming algae.

Post-transcriptional control of chloroplast gene expression.

Chloroplasts contain their own genome, organized as operons, which are generally transcribed as polycistronic transcriptional units. These primary transcripts are processed into smaller RNAs, which are further modified to produce functional RNAs. The RNA processing mechanisms remain largely unknown and represent an important step in the control of chloroplast gene expression.

[Patient-noninvasive mechanical ventilation interaction].

Noninvasive mechanical ventilation is one more step in the treatment of patients with acute respiratory failure. In addition to gas exchange disorders, its primary indication to initiate it is the presence of signs of respiratory muscles fatigue. To assure successful mechanical ventilation, the ventilator and patient must be synchronized, that is, the effort the patient makes to start inspiration is recognized by the ventilator and it quickly delivers gas flow, that the flow provided by the ventilator adapts to the flow need of the patient during delivery of gas phase and that the ventilator recognizes the cessation of inspiratory activity by the patient, ends the delivery of gas and opens the expiratory valve to allow the patient expiration.

FOXP1 status in splenic marginal zone lymphoma: a fluorescence in situ hybridization and immunohistochemistry approach.

Splenic marginal zone lymphoma (SMZL) is a well-recognized entity in which chromosomal aberrations seem to be potential markers in diagnosis, prognosis and disease monitoring. FOXP1 is a transcriptional regulator of B lymphopoiesis that is deregulated in some types of NHL. Translocation t(3;14)(p14;q32) has been described in marginal zone lymphomas but few series have studied FOXP1 involvement in SMZL.

Smart homes - current features and future perspectives.

In an ageing world, maintaining good health and independence for as long as possible is essential. Instead of hospitalization or institutionalization, the elderly and disabled can be assisted in their own environment 24h a day with numerous 'smart' devices. The concept of the smart home is a promising and cost-effective way of improving home care for the elderly and the disabled in a non-obtrusive way, allowing greater independence, maintaining good health and preventing social isolation.

A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy.

Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with approximately 80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm.

Experimental Design: We studied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)-treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification.

MicroRNA expression, chromosomal alterations, and immunoglobulin variable heavy chain hypermutations in Mantle cell lymphomas.

The contribution of microRNAs (miR) to the pathogenesis of mantle cell lymphoma (MCL) is not well known. We investigated the expression of 86 mature miRs mapped to frequently altered genomic regions in MCL in CD5(+)/CD5(-) normal B cells, reactive lymph nodes, and purified tumor cells of 17 leukemic MCL, 12 nodal MCL, and 8 MCL cell lines. Genomic alterations of the tumors were studied by single nucleotide polymorphism arrays and comparative genomic hybridization.

Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network.

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network.

Array-based DNA methylation profiling in follicular lymphoma.

Quantitative methylation profiling was performed using the Illumina GoldenGate Assay in untreated follicular lymphoma (FL) (164), paired pre- and post-transformation FL (20), benign haematopoietic (24) samples and purified B and T cells from two FL cases. Methylation values allowed separation of untreated FL samples from controls with one exception, based primarily on tumour-specific gains of methylation typically occurring within CpG islands. Genes that are targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2 were significantly over-represented among hypermethylated genes.

Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the Hospital Clinic of Barcelona experience.

Whether advances in treatment are prolonging survival of patients with chronic lymphocytic leukemia (CLL) is unclear. We analyzed presentation patterns and survival over time in 929 patients followed from 1980 to 2008 at the Hospital Clinic of Barcelona. The 5- and 10-year relative survival (adjusted for the expected survival in the general population) was estimated in patients seen in 2 periods of time: 1980-1994 (n = 451) and 1995-2004 (n = 365).

Forodesine has high antitumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis by induction of p73 and BIM.

Chronic lymphocytic leukemia (CLL) is an incurable disease derived from the monoclonal expansion of CD5(+) B lymphocytes. High expression levels of ZAP-70 or CD38 and deletions of 17p13 (TP53) and 11q22-q23 (ATM) are associated with poorer overall survival and shorter time to disease progression. DNA damage and p53 play a pivotal role in apoptosis induction in response to conventional chemotherapy, because deletions of ATM or p53 identify CLL patients with resistance to treatment.