RESUMEN
UNLABELLED: A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD34(+) cells and/or other major subsets of CD34(-) cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping. METHODS: We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease. RESULTS: Although MDS-associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low- versus high-grade cases. The most informative prognostic factors included the number of CD34(+) cells, presence of aberrant CD34(-)/CD117(+) precursors, decreased mature neutrophils and CD34(-) erythroid precursors, and increased numbers of CD36(-/lo) erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival. CONCLUSIONS: Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival.
Asunto(s)
Células de la Médula Ósea/inmunología , Inmunofenotipificación , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Células de la Médula Ósea/metabolismo , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/clasificación , Síndromes Mielodisplásicos/patología , Proyectos Piloto , PronósticoRESUMEN
Limited knowledge exists about the impact of specific genetic abnormalities on the proliferation of neoplastic B cells from chronic lymphoproliferative disorders (B-CLPDs). Here we analyze the impact of cytogenetic abnormalities on the proliferation of neoplastic B cells in 432 B-CLPD patients, grouped according to diagnosis and site of sampling, versus their normal counterparts. Overall, proliferation of neoplastic B cells highly varied among the different B-CLPD subtypes, the greatest numbers of proliferating cells being identified in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Compared with normal B cells, neoplastic B-CLPD cells showed significantly increased S + G(2)/M-phase values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukemia (B-CLL), BL, and some DLBCL cases. Conversely, decreased proliferation was observed in follicular lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), and some DLBCL patients; hairy cell leukemia, splenic marginal zone, and MALT-lymphoma patients showed S + G(2)/M phase values similar to normal mature B lymphocytes from LN. Interestingly, in B-CLL and MCL significantly higher percentages of S + G(2)/M cells were detected in BM versus PB and in LN versus BM and PB samples, respectively. In turn, presence of 14q32.3 gene rearrangements and DNA aneuploidy, was associated with a higher percentage of S + G(2)/M-phase cells among LPL/WM and B-CLL cases, respectively.
Asunto(s)
Linfocitos B/patología , Proliferación Celular , Aberraciones Cromosómicas , Trastornos Linfoproliferativos/patología , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Femenino , Humanos , Interfase , Cinética , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/genética , Masculino , Persona de Mediana EdadRESUMEN
B-cell chronic lymphocytic leukemia (B-CLL) is a well-defined clinical entity with heterogeneous molecular and cytogenetic features. Here, we analyze the impact of trisomy 12, del(13q), del(17p), and del(11q) as determined by interphase fluorescence in situ hybridization analysis of purified neoplastic B-CLL cells on their immunophenotype, DNA ploidy status and proliferative rate.Overall, 111 of 180 (62%) B-CLL cases studied displayed one (50%) or more (12%) genetic abnormalities, del(13q) (35%) being more frequently detected than trisomy 12 (23%) followed by del(11q) (9%) and del(17p) (8%). Trisomy 12 was associated with a higher frequency of DNA aneuploidy, stronger expression of CD19, CD20, CD22, CD24, CD27, CD79b, CD38, and sIg and lower reactivity for CD43 with respect to cytogenetically nonaltered cases. In turn, cases with del(13q) displayed greater reactivity for CD20, FMC7, CD27, CD22, CD5, and bcl2, while del(11q) was associated with brighter expression of CD38, FMC7, CD25, and sIg. Hierarchical clustering analysis of the immunophenotype of B-CLL cases with cytogenetic abnormalities allowed the identification of three different groups of patients with increasing frequencies of trisomy 12, del(11q), and del(13q). Remarkably, none of the cytogenetic abnormalities analyzed except coexistence of 13q- and 17p- had a clear impact on the proliferative index of B-CLL cells.