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Between 60 and 80% of patients with B-cell acute lymphoblastic leukemia show genetic abnormalities which influence the prognosis of the disease and the biology of the tumor.To analyze different genetic abnormalities in acute B lymphoblastic leukemia in children, its relationship with the immunophenotype and the proliferative rate compared with normal B cell precursors.We assessed immunophenotype, DNA content and proliferative rate in 44 samples by flow cytometry, and translocations t(9;22), t(12;21), t(4;11), and t(1;19) by RT-PCR. Using a hierarchical cluster analysis, we identified some immunophenotypic patterns associated to genetic abnormalities when compared with normal B cell precursors.DNA quantification showed that 21% of the cases had high hyperdiploidy and 47.7% has low hyperdiploidy. The presence of hyperdiploidy was associated with increased tumor proliferation and aberrant immunophenotypes, including abnormal expression of CD10, TdT, CD38, and CD45 and an increased size of the lymphoblasts. The presence of t(9;22) and t(12;21) discriminates normal cells from tumor cells with aberrant immunophenotype in the expression of CD19, CD22, CD13, CD33, CD38, CD34, and CD45.The aberrant immunophenotype profile detected in neoplastic cells along with abnormalities in the proliferative rate were significantly associated with DNA hyperdiploidy and clearly distinguished lymphoblasts with t(9;22) and t(12;21) from normal B cell precursors. The identification of these parameters is useful as a tool for classification and monitoring of these patients.

Introduccion La familia Ikaros de factores de transcripcion incluye genes cruciales en desarrollo hematopoyetico y que se han visto relacionados con el desarrollo de diferentes tipos de neoplasias hematologicas. Sin embargo, la compleja expresion de las isoformas en esta familia ha impedido cualquier utilidad clinica de las misma y esta el momento solo se ha caracterizado la presencia de ciertas isoformas en casos de leucemias y que, sin embargo, tambien aparecen en individuos sanos. Objetivo Basandonos en lo anterior, en el presente estudio se propone la estandarizacion una nueva metodologia que permita el estudio del conjunto completo de isoformas en la muestra, ya que todo parece indicar que es el desequilibrio de isoformas lo que se podria asociar a la enfermedad. Materiales y metodos Para ello se cuantificaron las regiones inter-exonicas de Ikaros a traves de qRT-PCR lo que permitio describir un perfil de expresion para el conjunto de isoformas presentes en cada paciente, que incluye diferencias de expresion de determinados exones, asi como presencia de procesamientos no canonicos. Resultados De esta manera hemos sido capaces de discriminar grupos de patologias, pudiendo discriminar grupos de leucemias linfoides agudas, leucemias linfoides cronicas, leucemias mieloides cronicas y mielomas multiples. Del mismo modo se encontraron diferencias entre los grupos de estirpe linfoides frente a los mieloides. Adicionalmente, se describio la evolucion del perfil de expresion de un paciente diagnosticado de leucemia mieloide cronica que evoluciono a leucemia linfoide aguda y que permitio observar variaciones moleculares en este tipo de patologias evolutivas. Conclusiones Estos resultados permiten inferir que el conjunto de isoformas Ikaros, y no la sobre-expresion de una sola de ellas, es caracteristico de la enfermedad y por tanto su estudio puede llegar a ser un buen marcador diagnostico. Ademas existen caracteristicas concretas, como la presencia de procesamientos no canonicos, que permitirian una implementacion rapida para el diagnostico de subgrupos dentro de algunas de las patologias y cuyo estudio es de alto interes ante la posibilidad de que supongan algun tipo de caracteristicas pronosticas.

A variety of genetic alterations are considered hallmarks of cancer development and progression. The Ikaros gene family, encoding for key transcription factors in hematopoietic development, provides several examples as genetic defects in these genes are associated with the development of different types of leukemia. However, the complex patterns of expression of isoforms in Ikaros family genes has prevented their use as clinical markers. In this study, we propose the use of the expression profiles of the Ikaros isoforms to classify various hematological tumor diseases. We have standardized a quantitative PCR protocol to estimate the expression levels of the Ikaros gene exons. Our analysis reveals that these levels are associated with specific types of leukemia and we have found differences in the levels of expression relative to five interexonic Ikaros regions for all diseases studied. In conclusion, our method has allowed us to precisely discriminate between B-ALL, CLL and MM cases. Differences between the groups of lymphoid and myeloid pathologies were also identified in the same way.

To assess the significance of chromosome translocation t(11;18)(q21;q21), B-cell lymphoma 10 (BCL-10) protein and Helicobacter pylori (H. pylori) infection in gastric mucosa-associated lymphoid tissue (MALT) lymphoma in Colombia.Fifty cases of gastric MALT lymphoma and their respective post-treatment follow-up biopsies were examined to assess the presence of the translocation t(11;18)(q21;q21) as identified by fluorescence in situ hybridization; to detect protein expression patterns of BCL10 using immunohistochemistry; and for evaluation of tumor histology to determine the correlation of these factors and resistance to H. pylori eradication.Infection with H. pylori was confirmed in all cases of gastric MALT lymphoma in association with chronic gastritis. Bacterial eradication led to tumor regression in 66% of cases. The translocation t(11;18)(q21;q21) was not present in any of these cases, nor was there evidence of tumor transformation to diffuse large B-cell lymphoma. Thirty-four percent of the patients showed resistance to tumor regression, and within this group, 7 cases, representing 14% of all those analyzed, were considered to be t(11;18)(q21;q21)-positive gastric MALT lymphomas. Protein expression of BCL10 in the nucleus was associated with the presence of translocation and treatment resistance. Cases that were considered unresponsive to therapy were histologically characterized by the presence of homogeneous tumor cells and a lack of plasmacytic differentiation. Responder cases exhibited higher cellular heterogeneity and a greater frequency of plasma cells.Both t(11;18)(q21;q21)-positive MALT lymphoma cases and those with nuclear BCL10 expression are considered resistant to H. pylori eradication. It is suggested that chronic antigenic stimulation is not a dominant event in resistant cases.