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Acquired Chromosome 11q Deletion Involving the Ataxia Teleangiectasia Locus in B-Cell Non-Hodgkin’s Lymphoma: Correlation With Clinicobiologic Features

From the Dipartimento di Scienze Biomediche e Terapie Avanzate, Sezione di Ematologia, and Dipartimento di Medicina Sperimentale e Diagnostica, Sezione di Microbiologia, University of Ferrara, Ferrara, and Istituto Dermopatico dell’Immacolata, IRCCS, Roma, Italy.

Address reprint requests to Antonio Cuneo, MD, Dipartimento di Scienze Biomediche, Sezione di Ematologia Università di Ferrara, Via Savonarola, 9 - 44100 Ferrara, Italy; email sse{at}dns.unife.it

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin’s lymphomas (NHL).

PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22–23 probe recognizing ATM sequences. Pertinent clinical data were collected.

RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/- more frequently had a complex karyotype (P = .01) and the AA karyotype (P = .04) compared with patients without ATM+/-. With the exception of a poor performance status (P = .001), no correlation was found between ATM+/-, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P < .0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P = .0004), along with performance status (P = .0006), serum lactate dehydrogenase level (P = .03), splenomegaly (P = .01), and histologic grade (P = .03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic importance as an independent variable in both histologic groups (P = .0001 and P = .016, respectively).

CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/- status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.

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