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A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia

¹ Servicios de Hematología, Hospital Infanta Leonor, Madrid;
² IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC;
³ Hospital Clínico Universitario de Salamanca;
⁴ Hospital Virgen Blanca, León;
⁵ Hospital del Río Hortega, Valladolid;
⁶ Hospital Virgen del Puerto, Plasencia, Cáceres;
⁷ Hospital Clínico Universitario, Valladolid;
⁸ Hospital General de Segovia;
⁹ Hospital del Bierzo, León;
¹⁰ Hospital Nuestra Señora de Sonsoles, Ávila and
¹¹ Hospital Morales Meseguer, Murcia, Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Unidad de Investigación, Hospital Universitario de Salamanca, Spain

Correspondence: Jesús María Hernández, Servicio de Hematología y, Departamento de Medicina, Hospital Universitario de, Salamanca Paseo San Vicente, 58, 37007 Salamanca, Spain., E-mail:jmhr{at}usal.es

Background: Among patients with B-cell chronic lymphoid leukemia, those with 13q14 deletion have a favorable outcome. However, whether the percentage of cells with 13q- influences the prognosis or the biological characteristics of this disease is unknown. We analyzed the clinico-biological characteristics and outcome of patients with B-cell chronic lymphoid leukemia with loss of 13q as the sole cytogenetic aberration.

Design and Methods: Three hundred and fifty patients with B-cell chronic lymphoid leukemia were studied. Clinical data were collected and fluorescence in situ hybridization and molecular studies were carried out. In addition, a gene expression profile was obtained by microarray-based analysis.

Results: In 109 out of the 350 cases (31.1%) loss of 13q was the sole cytogenetic aberration at diagnosis. In the subgroup of patients with 80% or more of cells with loss of 13q (18 cases), the overall survival was 56 months compared with not reached in the 91 cases in whom less than 80% of cells had loss of 13q (p< 0.0001). The variables included in the multivariate analysis for overall survival were the percentage of losses of 13q14 (p=0.001) and B symptoms (p=0.007). The time to first therapy in the group with 80% or more vs. less than 80% of losses was 38 months vs. 87 months, respectively (p=0.05). In the multivariate analysis the variables selected were unmutated status of IgV_H (p=0.001) and a high level of β₂microglobulin (p=0.003). Interestingly, these differences regarding overall survival and time to first therapy were also present when other cut-offs were considered. The gene expression profile of patients with a high number of losses in 13q14 showed a high proliferation rate, downregulation of apoptosis-related genes, and dysregulation of genes related to mitochondrial functions.

Conclusions: Patients with B-cell chronic lymphoid leukemia with a high number of losses in 13q14 as the sole cytogenetic aberration at diagnosis display different clinical and biological features: short overall survival and time to first therapy as well as more proliferation and less apoptosis. A quantification of the number of cells showing a genetic abnormality should, therefore, be included in the study of the prognostic factors of B-cell chronic lymphoid leukemia.

Key words: B chronic lymphoid leukemia, 13q14 deletion, outcome, proliferation, apoptosis.