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Haematologica. 2002 Jan;87(1):44-51.

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.

Author information

1
Institute of Hematology, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italy. sse@dns.unife.it

Abstract

BACKGROUND AND OBJECTIVES:

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.

DESIGN AND 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.

INTERPRETATION AND 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.

PMID:
11801464
[Indexed for MEDLINE]
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