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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Profiling three-dimensional nuclear telomeric architecture of myelodysplastic syndromes and acute myeloid leukemia defines patient subgroups
Clinical Cancer Research, Volume 18, No. 12, Year 2012
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Description
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 theAMLpatients 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. ©2012 AACR.
Authors & Co-Authors
Gadji, Macoura
Canada, Winnipeg
Research Institute in Oncology and Hematology
Senegal, Dakar
Université Cheikh Anta Diop de Dakar
Awe, Julius Adebayo
Canada, Winnipeg
Research Institute in Oncology and Hematology
Sweden, Skovde
Högskolan I Skövde
Rodrigues, Prerana
Canada, Winnipeg
Research Institute in Oncology and Hematology
Kumar, Rajat
Canada, Winnipeg
University of Manitoba
Houston, Donald S.
Canada, Winnipeg
University of Manitoba
Klewes, Ludger
Canada, Winnipeg
Research Institute in Oncology and Hematology
Diéye, Tandakha Ndiaye D.
Senegal, Dakar
Université Cheikh Anta Diop de Dakar
Rego, Eduardo Magalhães
Brazil, Sao Paulo
Universidade de São Paulo
Passetto, Roberto Falcão
Brazil, Sao Paulo
Universidade de São Paulo
De Oliveira, Fábio Morato
Brazil, Sao Paulo
Universidade de São Paulo
Mai, Sabine
Canada, Winnipeg
Research Institute in Oncology and Hematology
Statistics
Citations: 39
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1158/1078-0432.CCR-12-0087
ISSN:
10780432
e-ISSN:
15573265
Research Areas
Cancer
Health System And Policy
Study Design
Cohort Study
Study Approach
Quantitative