title: Profiling three-dimensional nuclear telomeric architecture of myelodysplastic syndromes and acute myeloid leukemia defines patient subgroups.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: The University of Manitoba, Manitoba Institute of Cell Biology, Cancer Care Manitoba, The Genomic Centre for Cancer Research and Diagnosis, Section of Hematoloy/Oncology, Department of Internal Medicine, The University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Macoura
authors.initials: M
authors.lastname: Gadji
authors.forename: Julius
authors.initials: J
authors.lastname: Adebayo Awe
authors.forename: Prerana
authors.initials: P
authors.lastname: Rodrigues
authors.forename: Rajat
authors.initials: R
authors.lastname: Kumar
authors.forename: Donald S
authors.initials: DS
authors.lastname: Houston
authors.forename: Ludger
authors.initials: L
authors.lastname: Klewes
authors.forename: Tandakha Ndiaye
authors.initials: TN
authors.lastname: Dièye
authors.forename: Eduardo Magalhães
authors.initials: EM
authors.lastname: Rego
authors.forename: Roberto Falcão
authors.initials: RF
authors.lastname: Passetto
authors.forename: Fábio Morato
authors.initials: FM
authors.lastname: de Oliveira
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000473:pathology; D002467:Cell Nucleus / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D042822:Genomic Instability; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D010865:Pilot Projects; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure*; D055815:Young Adult