Publication Date:
2012-11-16
Description:
Abstract 4577 Patients with chronic lymphocytic leukemia (CLL) whose tumor cells harbor 17p deletions (17p-) by fluorescent in-situ hybridization (FISH) or chromosome banding analysis (CBA) are considered to have a poor survival. The disease is usually refractory to conventional chemotherapy and alternative therapeutic approaches are generally recommended. There is, however, a degree of clinical heterogeneity within 17p- CLL patients, as a significant proportion of them remain asymptomatic for prolonged periods of time. The aim of this study was to determine the prognostic value of concomitant molecular abnormalities in patients with 17p- CLL. Clinical and laboratory data were collected from 76 patients with 17p- CLL, detected either at diagnosis (de novo deletions, 39 patients) or over the course of the disease (acquired deletions, 37 patients). The cut-off used to define a positive FISH result was 10%, and complex karyotype was defined as the presence of 3 or more aberrations by CBA. We performed Sanger sequencing of IGHV, TP53 (exons 4–9), NOTCH1 (exon 34) and SF3B1 (exons 14–18), as well as high resolution copy number analysis using a SNP-array platform (CN-SNP). Both CBA/FISH and molecular studies were performed on samples drawn on the same date. Main biological characteristics, including CD38 and ZAP-70 expression or beta2-microglobulin (B2M), were also recorded. We evaluated the impact of these variables on time to first treatment (TTFT) and overall survival (OS) from sampling. TTFT was only evaluated in patients with de novo 17p-, and OS was evaluated in the whole cohort. Optimal cut-offs for FISH, B2M and copy number aberrations (CNAs) were calculated using maximally selected rank statistics, and were ≥25%, ≥3.5 mg/dl and ≥3, respectively (maxstat package, R, version 2.15.0). TP53 mutations were detected in 28/60 (47%) patients, and were more frequent in patients with ≥25% 17p- cells by FISH (64% vs 32%, p=0.029). CN-SNP confirmed 17p losses in only 19/68 (28%) patients and 90% of them also had concurrent TP53 mutations. 17p- by CN-SNP were mostly detected in patients with ≥25% 17p- cells by FISH [11/16 (69%)], compared to 6/49 (12%) patients with
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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