Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia

Recent genomic studies have identified a wide range of novel genetic alterations that have substantially increased our knowledge of the biology of B- and T-progenitor acute lymphoblastic leukaemia (B-ALL, T-ALL) and defined new subtypes with prognostic and therapeutic relevance.1-4 Thanks to the use of transcriptome sequencing approaches, new cryptic fusion transcripts have been described, such as the ATP5L-KMT2A gene fusion, described by Gestrich et al. in a 14-month-old patient with aggressive B-ALL.5 ATP5L or ATP5MG (ATP Synthase Membrane Subunit G) catalyzes ATP synthesis during oxidative phosphorylation.6 This protein has recently been reported to interact with a SARS-CoV-2 protein.7 The histone lysine [K]-methyl transferase 2A (KMT2A) gene is a transcriptional coactivator that plays an essential role in regulating gene expression during early development and haematopoiesis. It is frequently rearranged to over 135 translocation partner genes in acute leukaemias.8 ATP5L is a novel KMT2A fusion partner not detectable by fluorescent in situ hybridization (FISH) or karyotype, due to the closeness of the two genes on chromosome 11q23. The Cleveland Medical Centre team found a reciprocal out-of-frame ATP5L-KMT2A rearrangement that juxtaposes the ATP5L exon 1 to the KMT2A exon 2, with the insertion of an extra nucleotide (G) at the fusion site.5 We sequenced leukaemic cells from eight adult ALL patients (two T-ALL, five B-ALL Philadelphia negative (Ph−) and one B-ALL Ph+; Table I) by a 199 gene RNA-sequencing panel (RNA-seq; Pan-Heme FusionPlex, ArcherDx Inc., Boulder, CO, USA).The study was supported by European Union Seventh Framework Programme (FP7/2007-2013) (GA 306242-NGS-PTL) and Associazione Italiana Leucemie (AIL)

Thermotolerant Campylobacter spp. in chicken and bovine meat in Italy: Prevalence, level of contamination and molecular characterization of isolates

Campylobacter species are common foodborne pathogens associated with cases of human gastroenteritis worldwide. A detailed understanding of the prevalence, contamination levels and molecular characteristics of Campylobacter spp. in cattle and chicken, which are likely the most important sources of human contamination, is imperative. A collection of 1243 poultry meat samples (665 chicken breasts and 578 chicken thighs) and 1203 bovine meat samples (689 hamburgers and 514 knife-cut meat preparations) were collected at retail outlets, in randomly selected supermarkets located in different Italian regions during one year. Of these samples, 17.38% of the poultry meat and 0.58% of the bovine meat samples tested positive for Campylobacter, of which 131 were Campylobacter jejuni (57.96%) and 95 were Campylobacter coli (42.03%). Campylobacter isolates were genotyped with the aim of assessing the genetic diversity, population structure, source distribution and Campylobacter transmission route to humans. All isolates were molecularly characterized by pulse field gel electrophoresis (PFGE), and further genotyped using multilocus sequence typing (MLST) and fla-SVR sequencing to gain better insight into the population structure. Antibiotic resistance was also investigate. The highest levels of resistance among chicken strains were observed for ciprofloxacin (88.25%), nalidixic acid (81.45%) and tetracycline (75.6%). PFGE analysis revealed 73 pulsotypes for C. jejuni and 54 pulsotypes for C. coli, demonstrating the existance of different and specific clones circulating in Italy. MLST of C.jejuni isolates mainly clustered in the CC353, CC354, CC21, CC206 and CC443; while C.coli isolates clustered only in CC828. The most common flaA alleles were 287 for C. jejuni and 66 for C. coli. Our study confirms that poultry meat is the main source of Campylobacteriosis, whereas red meat had a low level of contamination suggesting a minor role in transmission. The high presence of Campylobacter in retail chicken meat, paired with its increased resistance to antimicrobials with several multidrug resistance profiles detected, is alarming and represents a persistent threat to public health

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n= 95) or nilotinib (n= 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): antimicrobial-resistant Enterococcus faecalis in poultry

Enterococcus faecalis (E. faecalis) was identified among the most relevant antimicrobial-resistant (AMR) bacteria in the EU for poultry in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR E. faecalis can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 4 (Categories A, B and D; 0–5%, 5–10% and 1–10% probability of meeting the criteria, respectively) and the AHAW Panel is uncertain whether it meets the criteria in Sections 3 and 5 (Categories C and E, 33–66% and 33–66% probability of meeting the criteria, respectively). The animal species to be listed for AMR E. faecalis according to Article 8 criteria are mostly birds of the orders Galliformes and Anseriformes, but also mammals and reptiles can serve as reservoirs.info:eu-repo/semantics/publishedVersio

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): antimicrobial-resistant Staphylococcus pseudintermedius in dogs and cats

Staphylococcus pseudintermedius (S. pseudintermedius) was identified among the most relevant antimicrobial-resistant (AMR) bacteria in the EU for dogs and cats in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR S. pseudintermedius can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (30–90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2 and 4 (Categories A, B and D; 0–1%, 1–10% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel is uncertain whether it meets the criteria in Sections 3 and 5 (Categories C and E, 5–66% and 30–90% probability of meeting the criteria, respectively). The animal species to be listed for AMR S. pseudintermedius according to Article 8 criteria are mostly species belonging to the families of Canidae and Felidae, such as dogs and cats.info:eu-repo/semantics/publishedVersio

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): antimicrobial-resistant Rhodococcus equi in horses

Rhodococcus equi (R. equi) was identified among the most relevant antimicrobial-resistant (AMR) bacteria in the EU for horses in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR R. equi can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (10–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1 and 2 (Categories A and B; 5–10% and 10–33% probability of meeting the criteria, respectively), and the AHAW Panel is uncertain whether it meets the criteria in Sections 3, 4 and 5 (Categories C, D and E; 10–66% probability of meeting the criteria in all three categories). The animal species to be listed for AMR R. equi according to Article 8 criteria are mainly horses and other species belonging to the Perissodactyla and Artiodactyla orders.info:eu-repo/semantics/publishedVersio

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): antimicrobial-resistant Escherichia coli in dogs and cats, horses, swine, poultry, cattle, sheep and goats

Escherichia coli (E. coli) was identified among the most relevant antimicrobial-resistant (AMR) bacteria in the EU for dogs and cats, horses, swine, poultry, cattle, sheep and goats in previous scientific opinions. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with uncertain outcome. According to the assessment here performed, it is uncertain whether AMR E. coli can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33–66% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that the bacterium does not meet the criteria in Sections 1, 2, 3 and 4 (Categories A, B, C and D; 0–5%, 5–10%, 10–33% and 10–33% probability of meeting the criteria, respectively) and the AHAW Panel was uncertain whether it meets the criteria in Section 5 (Category E, 33–66% probability of meeting the criteria). The animal species to be listed for AMR E. coli according to Article 8 criteria include mammals, birds, reptiles and fish.info:eu-repo/semantics/publishedVersio

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): infection with Equine Herpesvirus-1

Equine Herpesvirus-1 infection has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of: Article 7 on disease profile and impacts, Article 5 on the eligibility of the disease to be listed, Article 9 for the categorisation of the disease according to disease prevention and control measures as in Annex IV and Article 8 on the list of animal species related to Equine Herpesvirus-1 infection. The assessment has been performed following a methodology composed of information collection and compilation, and expert judgement on each criterion at individual and collective level. The outcome is the median of the probability ranges provided by the experts, which indicates whether the criterion is fulfilled (66–100%) or not (0–33%), or whether there is uncertainty about fulfilment (33–66%). For the questions where no consensus was reached, the different supporting views are reported. According to the assessment performed, Equine Herpesvirus-1 infection can be considered eligible to be listed for Union intervention according to Article 5 of the Animal Health Law with 33–90% certainty. According to the criteria as in Annex IV of the AHL related to Article 9 of the AHL for the categorisation of diseases according to the level of prevention and control, it was assessed with less than 1% certainty that EHV-1 fulfils the criteria as in Section 1 (category A), 1–5% for the criteria as in Section 2 (category B), 10–66% for the criteria as in Section 3 (category C), 66–90% for the criteria as in Section 4 (category D) and 33–90% for the criteria as in Section 5 (category E). The animal species to be listed for EHV-1 infection according to Article 8(3) criteria are the species belonging to the families of Equidae, Bovidae, Camelidae, Caviidae, Cervidae, Cricetidae, Felidae, Giraffidae, Leporidae, Muridae, Rhinocerontidae, Tapiridae and Ursidae.info:eu-repo/semantics/publishedVersio

Assessment of the control measures of the Category A diseases of the Animal Health Law: prohibitions in restricted zones and risk-mitigating treatments for products of animal origin and other materials

EFSA received a mandate from the European Commission to assess the effectiveness of prohibitions of certain activities in restricted zones, and of certain risk mitigation treatments for products of animal origin and other materials with respect to diseases included in the Category A list in the Animal Health Law (Regulation (EU) 2016/429). This opinion belongs to a series of opinions where other disease-specific control measures have been assessed. In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of (i) prohibiting the movements of certain products, notably germinal products (semen, oocytes, embryos and hatching eggs), products of animal origin and animal by-products and feed of plant origin, hay and straw, and (ii) risk mitigation treatments for products of animal origin. In terms of semen, oocytes, embryos and hatching eggs, it was agreed that there was a lack of evidence particularly for embryos and oocytes reflected in a varying degree of uncertainty, whether these commodities could potentially contain the pathogen under consideration. The scenario assessed did not consider whether the presence of pathogen would lead to infection in the recipient animal. In terms of animal products, certain animal by-products and movement of feed of plant origin and straw, the assessment considered the ability of the commodity to transmit disease to another animal if exposed. For most pathogens, products were to some degree considered a risk, but lack of field evidence contributed to the uncertainty, particularly as potential exposure of ruminants to meat products is concerned. In terms of the risk mitigating treatments, recommendations have been made for several of these treatments, because the treatment description is not complete, the evidence is poor or inconclusive, or the evidence points to the treatment being ineffective.info:eu-repo/semantics/publishedVersio

Assessment of the control measures of category A diseases of the Animal Health Law: Infection with rinderpest virus (Rinderpest)

EFSA received a mandate from the European Commission to assess the effectiveness of control measures against diseases included in the Category A list according to Regulation (EU) 2016/429 on transmissible animal diseases ('Animal Health Law’). This opinion belongs to a series of opinions where these control measures are assessed, with this opinion covering the assessment of control measures for rinderpest (RP), the only animal disease to have been globally eradicated. In this opinion, the AHAW Panel reviewed the effectiveness of: (i) clinical and laboratory sampling procedures, (ii) monitoring period and (iii) the minimum radius of the protection and surveillance zone, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere. The transmission kernels used for the assessment of the minimum radius of the protection and surveillance zones are shown. Several scenarios for which control measures had to be assessed were agreed prior to the assessment. Considering that RP has been eradicated globally, a re-emergence that is not stopped in its early phases could have a devastating impact on animal health and the economy. The panel concludes that no suitable strategies are available to entirely mitigate the risk associated with granting derogations from killing of animals in an affected establishment or for animal movements. Therefore, the panel recommends to not grant any derogations. The monitoring period of 21 days was assessed as effective, except for the hypothetical first re-emergence of RP, when lack of awareness and diagnostic capability may extend the time to detection. It was concluded that the protection and the surveillance zones would contain 90% and > 99%, respectively, of the infections from an affected establishment. Enlarging the protection zone to 4 km would contain the disease spread with 95% probability.info:eu-repo/semantics/publishedVersio