RESUMEN
Philadelphia-positive (Ph(+)) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogeneous disease with a very poor prognosis. In this study, we analyzed the frequency of supernumerary Ph, trisomy 8, monosomy 7, and del(9p21) by FISH and its relationship with the characteristics of the disease, in 46 BCR/ABL(+) adult BCP-ALL patients. The frequency of supernumerary Ph, trisomy 8, monosomy 7 and del(9p21) was 30%, 20%, 15%, and 24%, respectively. Although all patients displayed a BII/common phenotype, supernumerary Ph and trisomy 8 were associated with higher expression of CD19 and CD22 and of CD19, CD34, CD45, and HLA-DR, respectively; in turn, cases with monosomy 7 showed lower CD19, CD22, CD34, and cCD79a and del(9p21)(+) blasts were CD13(-) and CD33(-). Overall, similar clinical and hematological features were observed at presentation, independently of the underlying genetic abnormalities. However, relapse-free survival (RFS) was significantly shorter in cases with supernumerary Ph, trisomy 8, and del(9p21), the latter being the most powerful independent prognostic factor for RFS.
Asunto(s)
Linfoma de Burkitt/genética , Proteínas de Fusión bcr-abl/genética , Heterogeneidad Genética , Inmunofenotipificación , Adulto , Anciano , Anciano de 80 o más Años , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/inmunología , Aberraciones Cromosómicas , ADN/genética , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo/métodos , Proteínas de Fusión bcr-abl/inmunología , Humanos , Hibridación Fluorescente in Situ/métodos , Interfase , Cariotipificación , Masculino , Persona de Mediana Edad , Ploidias , Factores de TiempoRESUMEN
In the present study we examined by Southern blot analysis the presence of deletions and rearrangements of the p16 tumor-suppressor gene in B cell non-Hodgkin's lymphomas (NHLs) in order to determine whether or not these changes can be related to a particular histological subtype and the different clinico-biological and prognostic characteristics of the disease. 103 untreated patients were enrolled in the study. Seven cases displayed alterations in the p16 gene: four cases with homozygous deletions and three with gene rearrangement. The presence of these abnormalities did not correlate with any specific histological subtype: three cases were small lymphocytic lymphomas (two of them reclassified as mantle cell lymphoma on the basis of the REAL classification), two diffuse large cell lymphomas and two small non-cleaved cell lymphomas (one of them considered to be a Burkitt-like lymphoma according to the REAL). These seven cases showed a trend towards worse prognostic indicators than the remaining patients, and this was confirmed in the survival analysis, since the presence of p16 gene abnormalities was associated with a shorter survival (10 vs 81 months, P = 0.0006). In the multivariate analysis, p16 abnormalities were selected as an independent prognostic factor together with the LDH and beta2-microglobulin. These findings support a role for the p16 gene in the pathogenesis of B cell NHLs and suggest an association of p16 abnormalities with aggressive forms of the disease that could be useful to predict the prognosis of patients.
Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Eliminación de Gen , Reordenamiento Génico , Genes Supresores de Tumor/genética , Linfoma de Células B/genética , Adulto , Humanos , Inmunofenotipificación , Linfoma de Células B/clasificación , Linfoma de Células B/mortalidad , Mutación , Pronóstico , Análisis de SupervivenciaRESUMEN
We have evaluated dyshemopoietic features in bone marrow (BM) samples obtained from healthy people aged over 50 without peripheral blood (PB) cytopenia patients and compared them with MDS patients. Control group displayed BM features of dyserythropoiesis and dysgranulopoiesis in up to 15 and 27% of the considered cell elements (P90) respectively, overlapping in part with MDS patients. Interobserver agreement in dyshemopoietic features was highest for BM blast cell and pathological sideroblast counts. An algorithm based on BM blast cell and pathological sideroblast counts that has been verified on 613 patients from different Spanish centers may be of help to improve reproducibility in Myelodysplastic syndrome (MDS) diagnosis.
Asunto(s)
Síndromes Mielodisplásicos/diagnóstico , Células Cultivadas , Humanos , Inmunofenotipificación , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/patologíaRESUMEN
The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 x 10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off" value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status.