title: Late appearance of the 11q22.3-23.1 deletion involving the ATM locus in B-cell chronic lymphocytic leukemia and related disorders. Clinico-biological significance.
abstract: OBJECTIVE
  Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated (ATM) locus (11q-/ATM+/-) are detected at diagnosis in 10-20% of cases of B-cell chronic lymphocytic leukemia (CLL) and are associated with a relatively aggressive disease. The aim of this study was to ascertain whether 11q-/ATM+/- may appear late during the course of the disease and to analyze its possible correlation with disease evolution.
  
  
  METHODS
  Eighty-two patients with CLL and related disorders, i.e. CLL/PL and prolymphocytic leukemia (PLL), without 11q- at diagnosis were sequentially ascertained at 1-2 year intervals by conventional cytogenetic analysis (CCA) and fluorescence in situ hybridization (FISH), using an ATM-specific probe.
  
  
  RESULTS
  Eight patients acquired a submicroscopic 11q deletion 13-43 months after diagnosis: the diagnosis at presentation was CLL in 3 cases, CLL/PL in 3 cases and PLL in 2 cases. A 13q14 deletion preceded the development of 11q- in four patients; additional aberrations included +12 (three cases), 17p13 deletion and 6q21 deletion (one case each). The acquisition of the 11q deletion was more frequently found in those patients presenting with CLL/PL and PLL than typical CLL (p=0.0016) and with splenomegaly (p=0.003). Follow-up data showed that karyotype evolution (p=0.009) and cytological transformation (p<0.001) were associated with the acquisition of this cytogenetic lesion. The variables predicting for a shorter survival in this series included the 11q deletion (p=0.03), along with other classical clinicobiological parameters (performance status, advanced stage, splenomegaly, elevated serum beta2 microglobulin and lactate dehydrogenase levels.
  
  
  CONCLUSIONS
  a) Submicroscopic 11q deletion involving the ATM locus may, in some instances, represent a secondary change in CLL, CLL/P and PLL, suggesting that sequential FISH analyses are necessary to detect this chromosome anomaly in some patients; b) the acquisition of 11q-/ATM deletion may play a role in determining cytological transformation and disease progression of CLL and related disorders.
authors.affiliation: Institute of Hematology, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italy. sse@dns.unife.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Renato
authors.initials: R
authors.lastname: Bigoni
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roberti
authors.forename: Antonella
authors.initials: A
authors.lastname: Bardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Milani
authors.forename: Claudia
authors.initials: C
authors.lastname: Minotto
authors.forename: Alessia
authors.initials: A
authors.lastname: Tieghi
authors.forename: Matteo
authors.initials: M
authors.lastname: Della Porta
authors.forename: Paola
authors.initials: P
authors.lastname: Agostini
authors.forename: Elisa
authors.initials: E
authors.lastname: Tammiso
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D015463:Leukemia, Prolymphocytic / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D013163:Splenomegaly / Q000209:etiology; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases