Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10(6), 1.08±0.11 × 10(5), 1.03±0.10 × 10(4), 1.02±0.09 × 10(3), 1.04±0.10 × 10(2) and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).

• MeSH
• Fusion Proteins, bcr-abl genetics   metabolism   MeSH
• DNA MeSH
• Gene Dosage MeSH
• Calibration MeSH
• Cloning, Molecular MeSH
• Real-Time Polymerase Chain Reaction standards   MeSH
• Humans MeSH
• Membrane Transport Proteins genetics   MeSH
• RNA, Messenger metabolism   MeSH
• Plasmids genetics   MeSH
• Escherichia coli Proteins genetics   MeSH
• Proto-Oncogene Proteins c-bcr genetics   MeSH
• Reference Standards MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants.

• MeSH
• Fusion Proteins, bcr-abl genetics   MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy   metabolism   MeSH
• Genetic Variation MeSH
• Calibration MeSH
• Humans MeSH
• Limit of Detection MeSH
• Polymerase Chain Reaction MeSH
• Gene Expression Regulation, Leukemic * MeSH
• Reproducibility of Results MeSH
• Gene Expression Profiling MeSH
• Protein-Tyrosine Kinases antagonists & inhibitors   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Geographicals
• Europe MeSH

BACKGROUND: Socioeconomic inequalities are increasingly recognised as an important public health issue, although their role in the leading causes of mortality in urban areas in Europe has not been fully evaluated. In this study, we used data from the INEQ-CITIES study to analyse inequalities in cause-specific mortality in 15 European cities at the beginning of the 21st century. METHODS: A cross-sectional ecological study was carried out to analyse 9 of the leading specific causes of death in small areas from 15 European cities. Using a hierarchical Bayesian spatial model, we estimated smoothed Standardized Mortality Ratios, relative risks and 95% credible intervals for cause-specific mortality in relation to a socioeconomic deprivation index, separately for men and women. RESULTS: We detected spatial socioeconomic inequalities for most causes of mortality studied, although these inequalities differed markedly between cities, being more pronounced in Northern and Central-Eastern Europe. In the majority of cities, most of these causes of death were positively associated with deprivation among men, with the exception of prostatic cancer. Among women, diabetes, ischaemic heart disease, chronic liver diseases and respiratory diseases were also positively associated with deprivation in most cities. Lung cancer mortality was positively associated with deprivation in Northern European cities and in Kosice, but this association was non-existent or even negative in Southern European cities. Finally, breast cancer risk was inversely associated with deprivation in three Southern European cities. CONCLUSIONS: The results confirm the existence of socioeconomic inequalities in many of the main causes of mortality, and reveal variations in their magnitude between different European cities.

• MeSH
• Bayes Theorem MeSH
• Poverty MeSH
• Health Status Disparities * MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Cause of Death trends   MeSH
• Spatial Analysis MeSH
• Cross-Sectional Studies MeSH
• Social Determinants of Health * MeSH
• Socioeconomic Factors MeSH
• Educational Status MeSH
• Cities economics   statistics & numerical data   MeSH
• Urban Health economics   statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• Cities economics   statistics & numerical data   MeSH