29 research outputs found
Retrospective evaluation of autologous bone marrow transplantation vs allogeneic bone marrow transplantation from an HLA identical related donor in acute myelocytic leukemia. A study of the European Cooperative Group for Blood and Marrow Transplantation (EBMT)
No full textWe analyzed retrospectively data from 1696 patients with AML transplanted in Europe from January 1987 to December 1992 and reported to the acute leukemia EBMT registry. Groups of patients were analyzed according to age (adults and children) and status at transplant (first remission = CR1; second remission CR2). (1) 1114 adult patients were transplanted in CR1; 516 received an allograft; 598 received an autograft. Following alloBMT, the transplant-related mortality (TRM) was significantly higher (27 vs 13%, P < 10(-4)), the relapse incidence (RI) lower (25 vs 52%, P < 10(-4)) and the leukemia-free survival (LFS) better (55 vs 42%, P = 0.006). Favorable prognostic factors for alloBMT were a FAB type other than M4-M5, a donor-recipient combination excluding a female donor to a male recipient, and a younger age. Favorable prognostic factors for ABMT were a younger age of the patients at time of transplant, the AML3 FAB type, and a longer interval from CR1 to ABMT. (2) 288 adult patients were transplanted in CR2: 98 received an allograft; 190 received an autograft. The TRM was higher following allogeneic BMT (32 vs 20%, P = 0.02) and the RI lower (42 vs 63%, P = 0.001). The LFS was not significantly different (alloBMT: 39%; ABMT: 30%, P = 0.22). (3) 242 children were transplanted in CR1; 129 received an allograft; 113 received an autograft. Following alloBMT, the RI was lower (25 + 5 vs 48 + 6%, P < 10(-4)), and the LFS better (68 vs 47%, P = 0.002), The use of TBI was a favorable prognostic factor in allografted patients with a lower RI and a better LFS. (4) The number of children transplanted in CR2 was too small for a comparative analysis. These results confirm that both allogeneic and autologous BMT are suitable curative approaches for AML, They favor the use of an HLA identical related allogeneic transplant when available, especially in younger patients, over ABMT with unpurged marrow. The role of purging in ABMT could not be addressed in this study
Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
No full textAddendum: search for ν μ → ν e oscillations with the OPERA experiment in the CNGS beam
No full textA first result of the search for ν ( )μ( ) → ν ( )e( ) oscillations in the OPERA experiment, located at the Gran Sasso Underground Laboratory, is presented. The experiment looked for the appearance of ν ( )e( ) in the CNGS neutrino beam using the data collected in 2008 and 2009. Data are compatible with the non-oscillation hypothesis in the three-flavour mixing model. A further analysis of the same data constrains the non-standard oscillation parameters θ (new) and suggested by the LSND and MiniBooNE experiments. For large values (>0.1 eV(2)), the OPERA 90% C.L. upper limit on sin(2)(2θ (new)) based on a Bayesian statistical method reaches the value 7.2 × 10(−3)
The impact of the source of stem cells on the outcome of Autologous Stem Cell Transplantation (ASCT) for patients with myelodysplastic syndrome or acute myeloid leukemia following MDS
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The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature
No full textAltres ajuts: SDCSD from School of Medicine, University of BarcelonaLong non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signatur
The role of highly conserved non-coding DNA sequences in vertebrate development and evolution
No full textPhDComparisons between vertebrate genome sequences, from mammals to fishes, have revealed thousands of conserved non-coding elements (CNEs) that are associated with developmental genes. Interestingly, the vast majority of these CNEs cannot be found in invertebrate genomes by sequence homology. As many CNEs have been demonstrated to act as enhancers in-vivo, it has been postulated that CNEs represent gene regulatory elements with crucial roles in aspects of development that are shared between vertebrates.
To trace the evolution of CNE sequences in vertebrates, a preliminary search for CNEs in the lamprey genome was conducted using the draft lamprey genome sequence. This thesis documents how the CNEs identified in lamprey have been used as a guide to ask questions about the function and evolution of CNEs in the vertebrate lineage. Through the combined use of comparative genomics and developmental biology techniques, including a newly developed reporter assay for sea lamprey embryos, crucial first steps have been taken toward systematically de-coding these ancient gene regulatory elements. Special attention is paid toward utilising the low sequence identity of lamprey CNEs for „phylogenetic footprinting‟, an approach which uncovers striking enrichment of CNEs for a set of motifs that are characteristic of Hox-regulated elements. These findings help to establish CNEs within a developmental and evolutionary context.School of Biological and Chemical Sciences Queen Mary University of London
Measurement of the neutrino velocity with the OPERA detector in the CNGS beam using the 2012 dedicated data
No full textIn spring 2012 CERN provided two weeks of a short bunch proton beam dedicated to the neutrino velocity measurement over a distance of 730 km. The OPERA neutrino experiment at the underground Gran Sasso Laboratory used an upgraded setup compared to the 2011 measurements, improving the measurement time accuracy. An independent timing system based on the Resistive Plate Chambers was exploited providing a time accuracy of ~1 ns. Neutrino and anti-neutrino contributions were separated using the information provided by the OPERA magnetic spectrometers. The new analysis profited from the precision geodesy measurements of the neutrino baseline and of the CNGS/LNGS clock synchronization. The neutrino arrival time with respect to the one computed assuming the speed of light in vacuum is found to be δt ν ≡ T OF c - T OF ν = (0.6±0.4 (stat.)±3.0 (syst.)) ns and δtν≡TOF c-TOFν = (1.7±1.4(stat.}±3.1(syst.) ns for νμ and νμ, respectively. This corresponds to a limit on the muon neutrino velocity with respect to the speed of light of -1.8 × 10-6 < (v ν - c)/c < 2.3 × 10-6 at 90% C.L. This new measurement confirms with higher accuracy the revised OPERA result. © 2013 SISSA.0OPERA Collaboration ;14 pp.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Search for oscillation with the OPERA experiment in the CNGS beam
No full textThe OPERA neutrino experiment in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in direct appearance mode in the nu_mu to nu_tau channel, the nu_tau signature being the identification of the tau-lepton created in its charged current interaction. The hybrid apparatus consists of a large mass emulsion film/lead target complemented by electronic detectors. It is placed in the high energy long-baseline CERN to LNGS neutrino beam (CNGS) 730 km away from the neutrino source. The observation of a first nu_tau candidate event was reported in 2010. In this paper, we present the status of the experiment based on the analysis of the data taken during the first two years of operation (2008-2009). The statistical significance of the one event observed so far is then assessed.The OPERA neutrino experiment in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in direct appearance mode in the channel, the signature being the identification of the -lepton created in its charged current interaction. The hybrid apparatus consists of a large mass emulsion film/lead target complemented by electronic detectors. It is placed in the high energy long-baseline CERN to LNGS neutrino beam (CNGS) 730 km away from the neutrino source. The observation of a first candidate event was reported in 2010. In this paper, we present the status of the experiment based on the analysis of the data taken during the first two years of operation (2008-2009). The statistical significance of the one event observed so far is then assessed
Evidence for appearance in the CNGS neutrino beam with the OPERA experiment
No full textThe OPERA experiment is designed to search for νμ→ντ oscillations in appearance mode, i.e., through the direct observation of the τ lepton in ντ-charged current interactions. The experiment has taken data for five years, since 2008, with the CERN Neutrino to Gran Sasso beam. Previously, two ντ candidates with a τ decaying into hadrons were observed in a subsample of data of the 2008–2011 runs. Here we report the observation of a third ντ candidate in the τ-→μ- decay channel coming from the analysis of a subsample of the 2012 run. Taking into account the estimated background, the absence of νμ→ντ oscillations is excluded at the 3.4 σ level.The OPERA experiment is designed to search for oscillations in appearance mode i.e. through the direct observation of the lepton in charged current interactions. The experiment has taken data for five years, since 2008, with the CERN Neutrino to Gran Sasso beam. Previously, two candidates with a decaying into hadrons were observed in a sub-sample of data of the 2008-2011 runs. Here we report the observation of a third candidate in the decay channel coming from the analysis of a sub-sample of the 2012 run. Taking into account the estimated background, the absence of oscillations is excluded at the 3.4 level
