Profiling Three-Dimensional Nuclear Telomeric Architecture of Myelodysplastic Syndromes and Acute Myeloid Leukemia Defines Patient Subgroups

Purpose: Myelodysplastic syndromes (MDS) are a group of disorders characterized by cytopenias, with a propensity for evolution into acute myeloid leukemias (AML). This transformation is driven by genomic instability, but mechanisms remain unknown. Telomere dysfunction might generate genomic instability leading to cytopenias and disease progression. Experimental Design: We undertook a pilot study of 94 patients with MDS (56 patients) and AML (38 patients). The MDS cohort consisted of refractory cytopenia with multilineage dysplasia (32 cases), refractory anemia (12 cases), refractory anemia with excess of blasts (RAEB) 1 (8 cases), RAEB2 (1 case), refractory anemia with ring sideroblasts (2 cases), and MDS with isolated del(5q) (1 case). The AML cohort was composed of AML-M4 (12 cases), AML-M2 (10 cases), AML-M5 (5 cases), AML-M0 (5 cases), AML-M1 (2 cases), AML-M4eo (1 case), and AML with multidysplasia-related changes (1 case). Three-dimensional quantitative FISH of telomeres was carried out on nuclei from bone marrow samples and analyzed using TeloView. Results: We defined three-dimensional nuclear telomeric profiles on the basis of telomere numbers, telomeric aggregates, telomere signal intensities, nuclear volumes, and nuclear telomere distribution. Using these parameters, we blindly subdivided the MDS patients into nine subgroups and the AML patients into six subgroups. Each of the parameters showed significant differences between MDS and AML. Combining all parameters revealed significant differences between all subgroups. Three-dimensional telomeric profiles are linked to the evolution of telomere dysfunction, defining a model of progression from MDS to AML. Conclusions: Our results show distinct three-dimensional telomeric profiles specific to patients with MDS and AML that help subgroup patients based on the severity of telomere dysfunction highlighted in the profiles. Clin Cancer Res; 18(12); 3293-304. (C) 2012 AACR.

The nitrogen sufficiency index underlying estimates of nitrogen fertilization requirements of common bean

Chlorophyll determination with a portable chlorophyll meter can indicate the period of highest N demand of plants and whether sidedressing is required or not. In this sense, defining the optimal timing of N application to common bean is fundamental to increase N use efficiency, increase yields and reduce the cost of fertilization. The objectives of this study were to evaluate the efficiency of N sufficiency index (NSI) calculated based on the relative chlorophyll index (RCI) in leaves, measured with a portable chlorophyll meter, as an indicator of time of N sidedressing fertilization and to verify which NSI (90 and 95 %) value is the most appropriate to indicate the moment of N fertilization of common bean cultivar Perola. The experiment was carried out in the rainy and dry growing seasons of the agricultural year 2009/10 on a dystroferric Red Nitosol, in Botucatu, São Paulo State, Brazil. The experiment was arranged in a randomized complete block design with five treatments, consisting of N managements (M1: 200 kg ha-1 N (40 kg at sowing + 80 kg 15 days after emergence (DAE) + 80 kg 30 DAE); M2: 100 kg ha-1 N (20 kg at sowing + 40 kg 15 DAE + 40 kg 30 DAE); M3: 20 kg ha-1 N at sowing + 30 kg ha-1 when chlorophyll meter readings indicated NSI < 95 %; M4: 20 kg ha-1 N at sowing + 30 kg ha-1 N when chlorophyll meter readings indicated NSI < 90 % and, M5: control (without N application)) and four replications. The variables RCI, aboveground dry matter, total leaf N concentration, production components, grain yield, relative yield, and N use efficiency were evaluated. The RCI correlated with leaf N concentrations. By monitoring the RCI with the chlorophyll meter, the period of N sidedressing of common bean could be defined, improving N use efficiency and avoiding unnecessary N supply to common bean. The NSI 90 % of the reference area was more efficient to define the moment of N sidedressing of common bean, to increase N use efficiency.