RESUMO
Monosomy 7 and del(7q) are associated with adverse features in myeloid malignancies. A 2.5-Mb commonly deleted segment (CDS) of chromosome band 7q22 is implicated as harboring a myeloid tumor suppressor gene (TSG); however, molecular analysis of candidate TSGs has not uncovered loss of function. To determine whether haploinsufficiency for the 7q22 CDS contributes to myeloid leukemogenesis, we performed sequential gene targeting to flank a region of orthologous synteny on mouse chromosome band 5A3 with loxP sites. We then generated Mx1-Cre, 5A3(fl) mutant mice and deleted the targeted interval in vivo. Although excision was inefficient, we confirmed somatic deletion of the 5A3 CDS in the hematopoietic stem cell compartment. Mx1-Cre, 5A3(fl) mice show normal hematologic parameters and do not spontaneously develop myeloid malignancies. The 5A3(fl) deletion does not cooperate with oncogenic Kras(G12D) expression, Nf1 inactivation, or retroviral mutagenesis to accelerate leukemia development and did not modulate responsiveness to antileukemia drugs. These studies demonstrate that it is feasible to somatically delete a large chromosomal segment implicated in tumor suppression in hematopoietic cell populations in vivo; however, our data do not support the hypothesis that the 7q22/5A3 CDS interval contains a myeloid TSG.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Leucemia Experimental/genética , Leucemia Mieloide/genética , Animais , Antineoplásicos/uso terapêutico , Sequência de Bases , Bandeamento Cromossômico , Mapeamento Cromossômico , Primers do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Marcação de Genes , Genes da Neurofibromatose 1 , Genes Supressores de Tumor , Engenharia Genética/métodos , Humanos , Leucemia Experimental/tratamento farmacológico , Leucemia Mieloide/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Transgênicos , Modelos Genéticos , Mutagênese Insercional , Proteínas Proto-Oncogênicas p21(ras)/genética , Recombinação Genética , Especificidade da EspécieRESUMO
Introducción. El objetivo del estudio es realizar un análisis retrospectivo de los componentes monoclonales nuevos detectados durante los años 2004, 2005 y 2006 en el Laboratorio del Carmen, dependiente del Servicio de Análisis Clínicos del Hospital Universitario Son Dureta. Material y métodos. El material son los datos obtenidos de los pacientes a los que se realiza un proteinograma en el Laboratorio del Carmen durante los años 20042006. Se realizó un estudio epidemiológico de tasa de incidencia de componentes monoclonales (CM) en Baleares, su distribución, edad y sexo de los pacientes. También se registraron los isotipos de CM, así como determinados parámetros analíticos como proteínas, hemoglobina, albúmina, creatinina, concentración de inmunoglobulinas. Se clasificaron los diagnósticos de los pacientes en función del tipo de patología más frecuente asociado al CM. Resultados. Durante estos años, se atendieron en el laboratorio del Carmen 696.115 pacientes pertenecientes al Área Sanitaria de Mallorca, realizándose 83.305 electroforesis de proteínas séricas (11,96%), de los cuales solo el 1,43% obtuvo un resultado de inmunofijación electroforética positivo. Resultados. La tasa de incidencia global es de 70,98 casos nuevos/100.000 habitantes/año. En el 62,8% de los pacientes con presencia de CM no consta ningún diagnóstico (AU)
Introduction. The aim of this study is to carry out a retrospective analysis of monoclonal gammopathies detected during the period of 2004, 2005 and 2006 in the El Carmen laboratory, which is part of the Clinical Laboratory of Son Dureta Hospital. We studied the most important aspects related to these patients and the study of the monoclonal gammopathies detected. Material and methods. An epidemiological study was carried out on all the data, in order to find the incidence of monoclonal gammopathies, as well as its distribution, and the age and sex of the patients. We also studied the immunochemical types of the monoclonal components, as well as some analytical parameters. The patient diagnosis was classified according to the most common pathology associated to the monoclonal component. Results. During these years, 696,115 patients belonging to the Healthy Area of Mallorca were seen in the El Carmen laboratory and 83,305 (11.96%) serum protein electrophoreses were performed. Results. Only 1.43% had a positive result with electrophoretic immunofixation. The overall incidence was 70.98 new cases/100,000 inhabitants/year. The majority of patients (62.8%) with a monoclonal component had no diagnosis (AU)