Biomedical subjects

Ana-Isabel Sáez

Publications and source records attributed to Ana-Isabel Sáez.

4 recordsLinked to original sources

PubMed2004

Building an outcome predictor model for diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) patients are treated using relatively homogeneous protocols, irrespective of their biological and clinical variability. Here we have developed a protein-expression-based outcome predictor for DLBCL. Using tissue microarrays (TMAs), we have analyzed the expression of 52 selected molecules in a series of 152 DLBCLs. The study yielded relevant information concerning key biological aspects of this tumor, such as cell-cycle control and apoptosis. A biological predictor was built with a training group of 103 patients, and was validated with a blind set of 49 patients. The predictive model with 8 markers can identify the probability of failure for a given patient with 78% accuracy. After stratifying patients according to the predicted response under the logistic model, 92.3% patients below the 25 percentile were accurately predicted by this biological score as "failure-free" while 96.2% of those above the 75 percentile were correctly predicted as belonging to the "fatal or refractory disease" group. Combining this biological score and the International Prognostic Index (IPI) improves the capacity for predicting failure and survival. This predictor was then validated in the independent group. The protein-expression-based score complements the information obtained from the use of the IPI, allowing patients to be assigned to different risk categories.

Adolescent↗

PubMed2003

Development of a real-time reverse transcription polymerase chain reaction assay for c-myc expression that allows the identification of a subset of c-myc+ diffuse large B-cell lymphoma.

Absence of a reliable method for determining the level of c-myc expression has impeded the analysis of its biological and clinical relevance in tumors. We have standardized the conditions for a real-time reverse transcription polymerase chain reaction analysis for c-myc expression, including the selection of an endogenous reference (18S rRNA), the adequate number of measurements for each sample (2 cDNA in triplicate), and suitable controls for determining inter- and intrarun variability (standard curve and calibrator). Subsequently, in a series of 56 non-Hodgkin's lymphomas, we analyzed the expression of c-myc mRNA, using real-time reverse transcription polymerase chain reaction, and of other functionally related proteins (bcl-6, p27, cyclin D3, and p53). As expected, all eight Burkitt's lymphoma cases analyzed had high levels of c-myc mRNA expression compared with that observed in reactive lymphoid tissue. There was a wider range of expression in diffuse large B-cell lymphoma, with 30% (15 of 48) of cases overexpressing c-myc. This overexpression was largely independent of c-myc translocations (4 of 5), as demonstrated by fluorescence in situ hybridization. In this large B-cell lymphoma series, a high level of c-myc expression predicted lower survival probability, irrespectively of the International Prognostic Index risk group classification. A slightly increased frequency of p53 inactivation was observed in the cases with c-myc overexpression, which suggests a growth advantage in lymphomas with concurrent deregulation of c-myc and p53. In addition, a moderate increase in bcl-6 protein expression was observed in the c-myc-positive cases, suggesting the existence of a complex interrelationship between these two genes. These findings suggest that c-myc may play a relevant role in the pathogenesis of a subset of large B-cell lymphoma and suggest the existence of additional regulatory mechanisms of c-myc expression to c-myc rearrangements.

B-Lymphocytes↗

PubMed2002

A short mutational hot spot in the first intron of BCL-6 is associated with increased BCL-6 expression and with longer overall survival in large B-cell lymphomas.

BCL-6 somatic mutations have been described in normal and tumoral B lymphocytes, associated with germinal center transit. We analyzed mutations in the major mutation cluster of BCL-6 in a series of 45 large B-cell lymphomas (LBCLs) and 15 Burkitt's lymphomas, and their relation to the level of BCL-6 expression and clinical outcome. Mutations in LBCL cases revealed the existence of two distinct, short mutational hot spots, spanning positions 106 to 127 and 423 to 443, in which the mutation frequency was higher than expected (P < 0.001). Mutations in the 423 to 443 subcluster were associated with an increased level of expression, although this was not the case with the 106 to 127 cluster. Additionally, LBCL cases characterized by the presence of mutations in the 423 to 443 cluster showed an increased overall survival (P < 0.05) when compared with the nonmutated LBCL cases in these positions. Burkitt's lymphoma cases showed a slightly lower frequency of mutations with a nonclustered distribution and lacked any relationship with the level of expression or any clinical characteristic. Findings from LBCLs suggest that the 423 to 443 cluster includes a regulatory region that is of importance for BCL-6 expression. Deregulation of BCL-6 expression caused by these mutations could play an important role in lymphoma genesis or progression.

DNA-Binding Proteins↗

PubMed2002

Analysis of octamer-binding transcription factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in lymphomas.

Oct1 and Oct2 are transcription factors of the POU homeo-domain family that bind to the Ig gene octamer sites, regulating B-cell-specific genes. The function of these transcription factors is dependent on the activity of B-cell-restricted coactivators such as BOB.1/OBF.1. Independent studies of the expression of these proteins in non-Hodgkin's lymphoma have been restricted to single markers, and most lack data concerning immunohistochemical expression. Thus, we have investigated the expression of Oct1, Oct2, and BOB.1/OBF.1 in human reactive lymphoid tissue and in a series of 140 Hodgkin and non-Hodgkin's lymphomas. None of these proteins was found to be restricted to B cells, although only B cells expressed high levels of all three markers. Additionally, germinal center B cells showed stronger Oct2 and BOB.1/OBF.1 staining. Consequently, most B-cell lymphomas showed reactivity for all three antibodies. Oct2 expression was significantly higher in germinal center-derived lymphomas, although other B-cell lymphomas also displayed a high level of Oct2 expression. Although T-cell lymphomas and Hodgkin's lymphomas expressed some of these proteins, they commonly exhibited less reactivity than B-cell lymphomas. Despite not being entirely cell-specific, the strong nuclear expression of Oct2 and BOB.1/OBF.1 by germinal center- derived lymphomas makes these antibodies a potentially useful tool in lymphoma diagnosis.

Antigens, CD20↗