¹Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Valencia, Spain

Correspondence: Dr JA Martinez-Climent, Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Avda. Blasco Ibañez 17, Valencia 46010, Spain. Fax: +34 96 3622238; E-mail: martinez_jos@gva.es

Received 10 April 2003; Accepted 5 January 2004; Published online 12 February 2004.

Abstract

In B-cell chronic lymphocytic leukemia (B-CLL), somatic mutation of IgV_H genes defines a subgroup with favorable prognosis, whereas the absence of IgV_H mutations is correlated with a worse outcome. Mutations of the BCL-6 gene are also observed in a subset of B-CLL, but the clinical significance of this molecular alteration remains uncertain. We examined the distribution of IgV_H and BCL-6 gene mutations in 95 well-characterized patients with Binet stage A B-CLL, and correlated them with clinical, laboratory, cytogenetic findings and disease progression. Mutations of the BCL-6 gene were observed only in cases harboring mutated IgV_H. Unexpectedly, coexistence of IgV_H and BCL-6 mutations was correlated with shorter treatment-free interval (TFI) compared to cases harboring only IgV_H mutation (median, 55 months vs not reached; P=0.01), resembling the clinical course of unmutated IgV_H cases (median TFI, 44 months). As expected, deletions of 17p13 (P53 locus) and 11q22 (ATM locus) were observed in cases with unmutated IgV_H, except one patient who showed mutations of both IgV_H and BCL-6. No other statistically significant differences were observed among the genetic subgroups. Our data indicate that BCL-6 mutations identify a subgroup of Binet stage A B-CLL patients with a high risk of progression despite the presence of mutated IgV_H gene.