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- Kotmayer, L, et al.
(författare)
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Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax
- 2023
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10−4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax–rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
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- Bedding, Timothy R., et al.
(författare)
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A multi-site campaign to measure solar-like oscillations in Procyon. II. mode frequencies
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 713:2, s. 935-949
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Tidskriftsartikel (refereegranskat)abstract
- We have analyzed data from a multi-site campaign to observe oscillations in the F5 star Procyon. The data consist of high-precision velocities that we obtained over more than three weeks with 11 telescopes. A new method for adjusting the data weights allows us to suppress the sidelobes in the power spectrum. Stacking the power spectrum in a so-called echelle diagram reveals two clear ridges, which we identify with even and odd values of the angular degree (l = 0 and 2, and l = 1 and 3, respectively). We interpret a strong, narrow peak at 446 mu Hz that lies close to the l = 1 ridge as a mode with mixed character. We show that the frequencies of the ridge centroids and their separations are useful diagnostics for asteroseismology. In particular, variations in the large separation appear to indicate a glitch in the sound-speed profile at an acoustic depth of similar to 1000 s. We list frequencies for 55 modes extracted from the data spanning 20 radial orders, a range comparable to the best solar data, which will provide valuable constraints for theoretical models. A preliminary comparison with published models shows that the offset between observed and calculated frequencies for the radial modes is very different for Procyon than for the Sun and other cool stars. We find the mean lifetime of the modes in Procyon to be 1.29(-0.49)(+0.55) days, which is significantly shorter than the 2-4 days seen in the Sun.
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- Delrez, Laetitia, et al.
(författare)
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Transit detection of the long-period volatile-rich super-Earth nu(2) Lupi d with CHEOPS
- 2021
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; :5, s. 775-787
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Tidskriftsartikel (refereegranskat)abstract
- Exoplanets transiting bright nearby stars are key objects for advancing our knowledge of planetary formation and evolution. The wealth of photons from the host star gives detailed access to the atmospheric, interior and orbital properties of the planetary companions. nu(2) Lupi (HD 136352) is a naked-eye (V = 5.78) Sun-like star that was discovered to host three low-mass planets with orbital periods of 11.6, 27.6 and 107.6 d via radial-velocity monitoring(1). The two inner planets (b and c) were recently found to transit(2), prompting a photometric follow-up by the brand new Characterising Exoplanets Satellite (CHEOPS). Here, we report that the outer planet d is also transiting, and measure its radius and mass to be 2.56 +/- 0.09 R-circle plus and 8.82 +/- 0.94 M-circle plus, respectively. With its bright Sun-like star, long period and mild irradiation (similar to 5.7 times the irradiation of Earth), nu(2) Lupi d unlocks a completely new region in the parameter space of exoplanets amenable to detailed characterization. We refine the properties of all three planets: planet b probably has a rocky mostly dry composition, while planets c and d seem to have retained small hydrogen-helium envelopes and a possibly large water fraction. This diversity of planetary compositions makes the nu(2) Lupi system an excellent laboratory for testing formation and evolution models of low-mass planets.
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- Kenanidis, Eustathios, et al.
(författare)
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Acetabular dysplasia
- 2018
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Ingår i: The adult hip - master case series and techniques. - Cham : Springer. - 9783319641775 - 9783319641751 ; , s. 107-213
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Bokkapitel (refereegranskat)
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- Maróti, Zoltán, et al.
(författare)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Tidskriftsartikel (refereegranskat)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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