Monitoring Of Bcr-abl Levels In Chronic Myeloid Leukemia Patients Treated With Imatinib In The Chronic Phase - The Importance Of A Major Molecular Response

Background: Real time PCR has become the most common technique to monitor BCR-ABL transcript levels of patients treated with kinase inhibitors. The aim of this study was to evaluate BCR-ABL levels of chronic myeloid leukemia patients treated with imatinib in the chronic phase and correlate the response to therapy and event-free survival. Methods: BCR-ABL levels were measured in peripheral blood cell samples using Real time PCR at diagnosis and then every 3 months after starting therapy with imatinib. Major molecular response was defined as a three-log reduction from the standardized baseline value. Major molecular response values were adjusted to international scale using a conversion factor of 1.19. The results are reported as a BCR-ABL/ABL ratio (%). Results: Hematological, major cytogenetic and complete cytogenetic responses were achieved by 57 (95%), 45 (75%) and 38 (63%) patients, respectively. Twenty-four out of sixty patients achieved a major molecular response (40%) in a median time of 8.5 months. Overall survival and event free survival were higher for patients with (100%) versus patients without (77%) a complete cytogenetic response (p-value = 0.01) at 48 months. Patients with complete cytogenetic response and major molecular response had a higher event free survival compared to patients with complete cytogenetic response but without major molecular response (p-value = 0.007). Conclusion: In conclusion, the prognostic impact of achieving complete cytogenetic response and a major molecular response and also the importance of molecular monitoring in the follow-up of chronic myeloid leukemia patients were demonstrated.333211215Melo, J.V., The molecular biology of chronic myeloid leukaemia (1996) Leukemia, 10 (5), pp. 751-756Wang, L., Pearson, K., Pillitteri, L., Ferguson, J.E., Clark, R.E., Serial monitoring of BCR-ABL by peripheral blood real-time polymerase chain reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic myeloid leukaemia (2002) Br J Haematol, 118 (3), pp. 771-777Muller, M.C., Gattermann, N., Lahaye, T., Deininger, M.W., Berndt, A., Fruehauf, S., Dynamics of BCR-ABL mRNA expression in firstline therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C (2003) Leukemia, 17 (12), pp. 2392-2400Branford, S., Hughes, T.P., Rudzki, Z., Monitoring chronic myeloid leukaemia therapy by real-time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics (1999) Br J Haematol, 107 (3), pp. 587-599Radich, J.P., Gooley, T., Bryant, E., Chauncey, T., Clift, R., Beppu, L., The significance of bcr-abl molecular detection in chronic myeloid leukemia patients late, 18 months or more after transplantation (2001) Blood, 98 (6), pp. 1701-1707Hughes, T.P., Kaeda, J., Branford, S., Rudzki, Z., Hochhaus, A., Hensley, M.L., Frequency of major molecular responses to imatinib or interferon-alpha plus cytarabine in newly diagnosed chronic myeloid leukemia (2003) N Engl J Med, 349 (15), pp. 1423-1432Press, R.D., Love, Z., Tronnes, A.A., Yang, R., Tran, T., Mongoue- tchokote, S., BCR-ABL mRNA levels at and after the time of a complete cytogenetic response predict the duration of CCR in imatinib mesylate-treated patients with CML (2006) Blood, 107 (11), pp. 4250-4256Cortes, J., Talpaz, M., O'Brien, S., Jones, D., Luthra, R., Shan, J., Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate (2005) Clin Cancer Res, 11 (9), pp. 3425-3432Iacobucci, I., Saglio, G., Rosti, G., Testoni, N., Pane, F., Amabile, M., Achieving a major molecular response at the time of a complete cytogenetic response (CCgR) predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients (2006) Clin Cancer Res, 12 (10), pp. 3037-3042Baccarani, M., Saglio, G., Goldman, J., Hochhaus, A., Simonsson, B., Appelbaum, F., Evolving concepts in the management of chronic myeloid leukemia: Recommendations from an expert panel on behalf of the European LeukemiaNet (2006) Blood, 108 (6), pp. 1809-1820Hughes, T., Deininger, M., Hochhaus, A., Branford, S., Radich, J., Kaeda, J., Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: Review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results (2006) Blood, 108 (1), pp. 28-37Branford, S., Cross, N.C., Hochhaus, A., Radich, J., Saglio, G., Kaeda, J., Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia (2006) Leukemia, 20 (11), pp. 1925-1930Cortes, J., Baccarani, M., Fea, G., (2008) A Phase III, Randomized, Openlabel Study of 400 Mg Versus 800 Mg of Imatinib Mesylate (IM) in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP), Using Molecular Endpoints: One Year Results of TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity) Study, , 50th ASH Annual Meeting and Exposition Online program and Abstracts. San Francisco, CABranford, S., Fletcher, L., Cross, N.C., Muller, M.C., Hochhaus, A., Kim, D.W., Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials (2008) Blood, 112 (8), pp. 3330-3338O'Brien, S.G., Guilhot, F., Larson, R.A., Gathmann, I., Baccarani, M., Cervantes, F., Imatinib compared with interferon and lowdose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia (2003) N Engl J Med, 348 (11), pp. 994-1004Marin, D., Milojkovic, D., Olavarria, E., Khorashad, J.S., de Lavallade, H., Reid, A.G., European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor (2008) Blood, 112 (12), pp. 4437-444

Rochechouart 2017-Drilling Campaign: First Results

No abstract available

What is the Oxygen Isotope Composition of Venus? The Scientific Case for Sample Return from Earth’s “Sister” Planet

Venus is Earth’s closest planetary neighbour and both bodies are of similar size and mass. As a consequence, Venus is often described as Earth’s sister planet. But the two worlds have followed very different evolutionary paths, with Earth having benign surface conditions, whereas Venus has a surface temperature of 464 °C and a surface pressure of 92 bar. These inhospitable surface conditions may partially explain why there has been such a dearth of space missions to Venus in recent years.The oxygen isotope composition of Venus is currently unknown. However, this single measurement (Δ17O) would have first order implications for our understanding of how large terrestrial planets are built. Recent isotopic studies indicate that the Solar System is bimodal in composition, divided into a carbonaceous chondrite (CC) group and a non-carbonaceous (NC) group. The CC group probably originated in the outer Solar System and the NC group in the inner Solar System. Venus comprises 41% by mass of the inner Solar System compared to 50% for Earth and only 5% for Mars. Models for building large terrestrial planets, such as Earth and Venus, would be significantly improved by a determination of the Δ17O composition of a returned sample from Venus. This measurement would help constrain the extent of early inner Solar System isotopic homogenisation and help to identify whether the feeding zones of the terrestrial planets were narrow or wide.Determining the Δ17O composition of Venus would also have significant implications for our understanding of how the Moon formed. Recent lunar formation models invoke a high energy impact between the proto-Earth and an inner Solar System-derived impactor body, Theia. The close isotopic similarity between the Earth and Moon is explained by these models as being a consequence of high-temperature, post-impact mixing. However, if Earth and Venus proved to be isotopic clones with respect to Δ17O, this would favour the classic, lower energy, giant impact scenario.We review the surface geology of Venus with the aim of identifying potential terrains that could be targeted by a robotic sample return mission. While the potentially ancient tessera terrains would be of great scientific interest, the need to minimise the influence of venusian weathering favours the sampling of young basaltic plains. In terms of a nominal sample mass, 10 g would be sufficient to undertake a full range of geochemical, isotopic and dating studies. However, it is important that additional material is collected as a legacy sample. As a consequence, a returned sample mass of at least 100 g should be recovered.Two scenarios for robotic sample return missions from Venus are presented, based on previous mission proposals. The most cost effective approach involves a “Grab and Go” strategy, either using a lander and separate orbiter, or possibly just a stand-alone lander. Sample return could also be achieved as part of a more ambitious, extended mission to study the venusian atmosphere. In both scenarios it is critical to obtain a surface atmospheric sample to define the extent of atmosphere-lithosphere oxygen isotopic disequilibrium. Surface sampling would be carried out by multiple techniques (drill, scoop, “vacuum-cleaner” device) to ensure success. Surface operations would take no longer than one hour.Analysis of returned samples would provide a firm basis for assessing similarities and differences between the evolution of Venus, Earth, Mars and smaller bodies such as Vesta. The Solar System provides an important case study in how two almost identical bodies, Earth and Venus, could have had such a divergent evolution. Finally, Venus, with its runaway greenhouse atmosphere, may provide data relevant to the understanding of similar less extreme processes on Earth. Venus is Earth’s planetary twin and deserves to be better studied and understood. In a wider context, analysis of returned samples from Venus would provide data relevant to the study of exoplanetary systems

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

Potassic-ultrapotassic mafic rocks delineate two-lithospheric mantle blocks beneath the southern Peruvian Altiplano

Geology, v. 33, n. 7, p. 601-604, 2005. http://dx.doi.org/10.1130/G21643.1International audienc

Sulfide petrology and highly siderophile element geochemistry of abyssal peridotites: a coupled study of samples from the Kane Fracture Zone (45°23′N, MARK area, Atlantic Ocean)

Nineteen samples from the Kane Fracture Zone have been studied for sulfide mineralogy and analyzed for S, Se, platinum-group elements (PGE), and Au to assess the effect of refertilization processes on the PGE systematics of abyssal peridotites. The lherzolites show broadly chondritic PGE ratios and sulfide modal abundances (0.01 to 0.03 wt%) consistent with partial melting models, although the few pyroxene-hosted sulfide inclusions and in situ LAM-ICPMS analyses provide evidence for in situ mobilization of a Cu-Ni–rich sulfide partial melt. The most refractory harzburgites (spinel Cr# > 29) are almost devoid of magmatic sulfides and show uniformly low PdN/IrN (<0.5) for variable PtN/IrN (0.8 to 1.2). The compatible behavior of Os, Ir, Ru, Rh, and Pt reflects the presence of primary Os-Ru alloys. Some harzburgites displaying petrographic evidence for refertilization by incremental melts en route to the surface are enriched in sulfides (up to 0.1 wt%). Some of these sulfides are concentrated in small veinlets of clinopyroxene and spinel crystallized from these melts. These S-rich harzburgites display superchondritic PdN/IrN (up to 2.04) positively correlated with sulfide modal contents. It is concluded that refertilization processes resulting in precipitation of metasomatic sulfides may significantly enhance Pd concentrations of abyssal peridotites while marginally affecting Pt (PtN/IrN ≤ 1.24) and Rh (RhN/IrN ≤ 1.23) as well. When the effects of such processes are screened out, our database suggests PGE relative abundances in the DMM (Depleted MORB Mantle; MORB: Mid-Ocean Ridge) within the uncertainty range of chondritic meteorites, without evidence of superchondritic Pt/Ir and/or Rh/Ir ratios