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- Andersen, Christen L., et al.
(författare)
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A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia
- 2013
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 162:4, s. 498-508
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P=0.06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P=0.03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P=0.006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.
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- Boluda, C. G., et al.
(författare)
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Evaluating methodologies for species delimitation : the mismatch between phenotypes and genotypes in lichenized fungi (Bryoria sect. Implexae, Parmeliaceae)
- 2019
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Ingår i: Persoonia. - : RIJKSHERBARIUM. - 0031-5850 .- 1878-9080. ; 42, s. 75-100
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Tidskriftsartikel (refereegranskat)abstract
- In many lichen-forming fungi, molecular phylogenetic analyses lead to the discovery of cryptic species within traditional morphospecies. However, in some cases, molecular sequence data also questions the separation of phenotypically characterised species. Here we apply an integrative taxonomy approach - including morphological, chemical, molecular, and distributional characters - to re-assess species boundaries in a traditionally speciose group of hair lichens, Bryoria sect. Implexae. We sampled multilocus sequence and microsatellite data from 142 specimens from a broad intercontinental distribution. Molecular data included DNA sequences of the standard fungal markers ITS, IGS, GAPDH, two newly tested loci (FRBi15 and FRBi16), and SSR frequencies from 18 microsatellite markers. Datasets were analysed with Bayesian and maximum likelihood phylogenetic reconstruction, phenogram reconstruction, STRUCTURE Bayesian clustering, principal coordinate analysis, haplotype network, and several different species delimitation analyses (ABGD, PTP, GMYC, and DISSECT). Additionally, past population demography and divergence times are estimated. The different approaches to species recognition do not support the monophyly of the 11 currently accepted morphospecies, and rather suggest the reduction of these to four phylogenetic species. Moreover, three of these are relatively recent in origin and cryptic, including phenotypically and chemically variable specimens. Issues regarding the integration of an evolutionary perspective into taxonomic conclusions in species complexes, which have undergone recent diversification, are discussed. The four accepted species, all epitypified by sequenced material, are Bryoria fuscescens, B. glabra, B. kockiana, and B. pseudofuscescens. Ten species rank names are reduced to synonymy. In the absence of molecular data, they can be recorded as the B. fuscescens complex. Intraspecific phenotype plasticity and factors affecting the speciation of different morphospecies in this group of Bryoria are outlined.
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