title: Telomere shortening in patients with plasma cell disorders.
abstract: OBJECTIVE
  Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
  
  
  METHODS
  Thirty-one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.
  
  
  RESULTS
  TRF analysis in total MM patients showed a mean TRF peak value (5.20 +/- 0.35 kb) shorter than those observed in controls (8.5 +/- 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = -0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 +/- 1.98%) with respect to MGUS (6.12 +/- 1.87%) and normal BM cells (2.00 +/- 0.93%) (P < 0.001).
  
  
  CONCLUSIONS
  MM patients showed a significant reduction in TL (> 60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.
authors.affiliation: Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina. acottliar@yahoo.com.ar
authors.forename: Alejandra
authors.initials: A
authors.lastname: Cottliar
authors.forename: Estela
authors.initials: E
authors.lastname: Pedrazzini
authors.forename: Claudia
authors.initials: C
authors.lastname: Corrado
authors.forename: María Inés
authors.initials: MI
authors.lastname: Engelberger
authors.forename: Marina
authors.initials: M
authors.lastname: Narbaitz
authors.forename: Irma
authors.initials: I
authors.lastname: Slavutsky
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D010265:Paraproteinemias / Q000235:genetics* / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D016615:Telomere / Q000648:ultrastructure*