Impacts of soil conditions and light availability on natural regeneration of Norway spruce Picea abies (L.) H. Karst. in low-elevation mountain forests

& Key message Natural regeneration of P. abies (L.) H. Karst. may reach high densities in lower mountain elevations. The highest densities were found in sites with moderate light availability, with low pH, and not near the riverbank. However, age-height classes differed in the predicted magnitude of response, but were consistent in response directions. Mosses and understory species typical of coniferous forests were positively correlated with regeneration density. & Context Norway spruce Picea abies (L.) H. Karst. in Central Europe is at risk under climate change scenarios, particularly in mountain regions. Little is known about the impact of environmental factors on the natural regeneration of P. abies in lowelevation mountain forests. & Aims We aimed to assess impacts of distance from the riverbank, soil pH, and light availability on natural P. abies regeneration. We hypothesized that (1) natural P. abiesregeneration would depend on light availability and soil pH and (2) there are understory plant species which may indicate the microsites suitable for natural regeneration of P. abies. & Methods The study was conducted in the Stołowe Mountains National Park (SW Poland, 600–800 m a.s.l.). We established 160 study plots (25 m2 ) for natural regeneration, light availability, soil pH, and understory vegetation assessment

Drivers of treeline shift in different European mountains

A growing body of evidence suggests that processes of upward treeline expansion and shifts in vegetation zones may occur in response to climate change. However, such shifts can be limited by a variety of non-climatic factors, such as nutrient availability, soil conditions, landscape fragmentation and some species-specific traits. Many changes in species distributions have been observed, although no evidence of complete community replacement has been registered yet. Climatic signals are often confounded with the effects of human activity, for example, forest encroachment at the treeline owing to the coupled effect of climate change and highland pasture abandonment. Data on the treeline ecotone, barriers to the expected treeline or dominant tree species shifts due to climate and land use change, and their possible impacts on biodiversity in 11 mountain areas of interest, from Italy to Norway and from Spain to Bulgaria, are reported. We investigated the role of environmental conditions on treeline ecotone features with a focus on treeline shift. The results showed that treeline altitude and the altitudinal width of the treeline ecotone, as well as the significance of climatic and soil parameters as barriers against tree species shift, significantly decreased with increasing latitude. However, the largest part of the commonly observed variability in mountain vegetation near the treeline in Europe seems to be caused by geomorphological, geological, pedological and microclimatic variability in combination with different land use history and present socio-economic relation Vegetation zone shift · Climate change · Climate models · Treeline ecotone · European mountains · Ecosystem service

Durable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)

CONCLUSIONS MDS are serious life-threatening hematologic malignancies in which a heterogeneous group of clonal disorders results in ineffective hematopoiesis. An unmet need remains for new therapies for patients (pts) with LR-MDS who are red blood cell transfusion dependent (RBC-TD) and R/R to or ineligible for ESAs. Imetelstat, an oligonucleotide, is a first-in-class telomerase inhibitor that targets cells with high telomerase activity by direct binding to the RNA template of telomerase. In the IMerge phase 3 trial, imetelstat produced higher rates of TI for ≥8 weeks, ≥24 weeks, and ≥1 year (39.8%, 28.0%, and 17.8%) than placebo (15.0%, 3.3%, and 1.7%) in pts with non-del(5q) LR-MDS that was RBC-TD, R/R to/ineligible for ESAs, and naïve to lenalidomide or hypomethylating agents (HMAs; Platzbecker et al. EHA 2023. Abstr S165). We report characteristics and clinical benefit for pts with sustained TI for ≥1 year from this trial. IMerge (MDS3001, NCT02598661) is a global, double-blind, randomized, placebo-controlled, phase 3 trial of imetelstat in RBC-TD, ESA-R/R, non-del 5(q) lenalidomide/HMA-naïve LR-MDS. The primary end point was 8-week TI rate; secondary end points included safety, 24-week TI, duration of response, hematologic improvement, and MDS response. Exploratory end points included assessment of cytogenetic response and mutational status with clinical response. The proportion of pts with>1-year TI and other binary end points, were summarized with percentage and 95% 2-sided exact Clopper-Pearson CI. The Kaplan-Meier method was used to estimate the distribution of TI. Of 118 pts receiving imetelstat, 21 (17.8%; 95% CI, 11.4-25.9) achieved ≥1-year sustained TI, representing 45% of ≥8-week TI (21 of 47 pts) and 64% of ≥24-week TI (21 of 33 pts); of 60 pts receiving placebo plus supportive care, 1 (1.7%; 95% CI, 0-8.9) achieved ≥1-year TI. Of the ≥1-year TI imetelstat responders, 15/21 (71.4%) had ring sideroblasts, as did the 1 placebo pt. The median prior RBC transfusion burden was 6 U over 8 weeks (range, 4-9 U) for the imetelstat group and 5 U for the placebo pt. Additional baseline characteristics are in the table. Pts received imetelstat for a median of 101.1 weeks (range, 75.1-163.9 weeks) and a median of 24 cycles (range, 18-41 cycles). The median duration of TI for imetelstat ≥1-year TI responders was 123 weeks (95% CI, 80.4 to not evaluable); the median increase in hemoglobin during the longest TI interval was 5.18 g/dL (range, 2.67-13.76 g/dL) for the imetelstat group vs 1.67 g/dL for the placebo pt. After a median follow-up of 125 weeks, none of the patients with ≥1 year TI on either arm progressed to acute myeloid leukemia (AML). Of the pts receiving imetelstat, 7 had an abnormal karyotype at baseline, of which 6 had reduction in the cytogenetic abnormal clones (4 with cytogenetic complete response and 2 with cytogenetic partial response by independent review committee). Mutation data were available for 18 pts receiving imetelstat, all with SF3B1 mutations present at baseline, and multiple of these pts concurrently had TET2, DNMT3A, ASXL1, or JAK2 mutations. The maximal reduction ranged from −6% to −100% in SF3B1 variant allele frequency (VAF) in these pts, and 13 of 18 (72.2%) achieved ≥50% VAF reduction, including 7 with complete elimination of the VAF. Reduction in other concurrent mutations was also observed in these pts. Safety was consistent with that previously reported; most frequent adverse events were reversible grade 3 or 4 thrombocytopenia and neutropenia. At the time of data cutoff (May 10, 2023), 13 pts receiving imetelstat and the pt receiving placebo were ongoing (Figure); of the 8 who discontinued treatment, 7 had loss of response, and 1 was due to adverse event. Analyses for progression-free and overall survival were not evaluable as of this cutoff date (insufficient follow-up). Treatment with imetelstat resulted in ≥1-year sustained, continuous TI in 17.8% of pts in the IMerge phase 3 trial. In this ESA-R/R/ineligible population with a high prior transfusion burden, a reduction to 0 RBC transfusions for ≥1 year represents an opportunity to achieve relief from iron overload and other transfusion associated complications, and decreased demand on already limited blood product supply. Furthermore, durable TI and meaningful reductions in mutational burden suggest imetelstat may have disease-modifying activity