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A high number of losses in 13ql4 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia

AuthorsHernández, José Ángel; Rodríguez-Vicente, Ana Eugenia; Benito, Rocío; Fontanillo, Celia ; García, Juan L. ; De Las Rivas, Javier ; Gutiérrez, Norma Carmen; San Miguel, Jesús F. ; Hernández, Jesús M.
Issue Date2009
PublisherFerrata Storti Foundation
CitationHaematologica 94(3): 364-371 (2009)
Abstract[Background]: Among patients with B-cell chronic lymphoid leukemia, those with 13ql4 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 ($ < 0.0001). The variables included in the multivariate analysis for overall survival were the percentage of losses of 13ql4 (/?=0.001) and B symptoms (/?=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 (/?=0.05). In the multivariate analysis the variables selected were unmutated status of IgVH (/?=0.001) and a high level of microglobulin (/?=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 13ql4 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 13ql4 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 apop- tosis. 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. © 2009 Ferrata Storti Foundation.
Description8 páginas, 3 figuras, 3 tablas.-- et al.
Publisher version (URL)http://dx.doi.org/10.3324/haematol.13862
Identifiersdoi: 10.3324/haematol.13862
issn: 0390-6078
e-issn: 1592-8721
Appears in Collections:(IBMCC) Artículos
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