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.
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.


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 beta(2)microglobulin (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.
Hernández
José Angel
JA
Servicios de Hematología, Hospital Infanta Leonor, Madrid, Spain.
Rodríguez
Ana Eugenia
AE
González
Marcos
M
Benito
Rocío
R
Fontanillo
Celia
C
Sandoval
Virgilio
V
Romero
Mercedes
M
Martín-Núñez
Guillermo
G
de Coca
Alfonso García
AG
Fisac
Rosa
R
Galende
Josefina
J
Recio
Isabel
I
Ortuño
Francisco
F
García
Juan Luis
JL
de las Rivas
Javier
J
Gutiérrez
Norma Carmen
NC
San Miguel
Jesús F
JF
Hernández
Jesús María
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis