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.
Background The first case of COVID-19 infection was diagnosed in Brazil 26th February 2020. By March 16th, physical distancing and confinement measures were implemented by the Brazilian government. Little is known about how these measures were followed up by the Brazilian people and their impact on daily routine. Methods In early April 2020, using an online platform, we organized an online survey among adults living in Brazil about their COVID-19 preventive behavior and impact on their daily routine. Results Data from 23,896 respondents were analyzed (mean age: 47.4 years). Due to COVID-19 restrictions, half (51.1%) of the professionals reported working from home. Regular handwashing was practiced by 98.7% of participants; 92.6% reported adhering to the 1.5-2 m physical distancing rule, but only 45.5% wore a face mask when going outside. While 29.3% of respondents found it relatively easy to stay at home, indoor confinement was extremely difficult for 7.9% of participants. Moreover, 11% of participants were extremely worried about their health during the COVID-19 epidemic. Younger people, male, persons living in a rural area/village or popular neighbourhoods, students and workers reported less preventive behaviour. Conclusion Restrictive measures markedly affected the daily and professional routines of Brazilians. Participants showed a satisfactory level of adherence to national COVID-19 prevention guidelines. Qualitative and follow-up studies are needed to monitor the impact of COVID-19 in the Brazilian society.
Summary Although biological similarities have been described among monoclonal B‐cell lymphocytosis (MBL) and chronic lymphocytic leukaemia (CLL), the relationships between these two conditions are not fully understood, and new epidemiological studies in different populations and different countries continue to be reported. Here, we investigated 167 first‐degree relatives from 42 families of patients with non‐familial (sporadic) CLL, using four‐colour flow cytometry. MBL was found in seven of 167 subjects (4·1%). Monoclonality was detected in all cases either by light‐chain restriction or by polymerase chain reaction. Fluourescence in situ hybridization did not show any chromosomal abnormality. The prevalence of MBL according to age was 0 (0/54) in individuals aged less than 40 years, 2·5% (2/81) between 40 and 60 years, and 15·6% (5/32) in individuals over 60 years. The prevalence of MBL cases in individuals over 60 years was similar to that found in familial CLL relatives at the same age group. This suggests that in older first‐degree relatives of patients with sporadic CLL, the risk of MBL detection is as high as in older first‐degree relatives from CLL families, which could render these individuals belonging to ‘sporadic CLL families’ as susceptible as individuals from ‘familial CLL’ to the development of clinical CLL.
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