RESUMO
Acute promyelocytic leukemia (APL) is characterized by the chromosomal translocation t(15;17)(q24;q21), raising two hybrid genes: PML::RARA and RARA::PML. There is a biased clonal evolution in APL since imbalances affecting the der(15) chromosome (the one that carries the transforming PML::RARA gene) have never been reported; instead, imbalances of the der(17), mainly in form of an ider(17)(q10), have been repeatedly documented. We here present two cases with APL who acquired an ider(17)(q10) as a secondary chromosomal change. The presence of the ider(17)(q10) implies several genomic consequences with potential to fuel tumor progression: (1) a duplication of the hybrid gene RARA::PML; (2) a cumulative haploinsufficiency for tumor suppressor genes located in the 17p arm; and (3) a cumulative triplosensitivity of genes located in 17q10âRARA::PMLâ15qter. Both our patients were treated following the PETHEMA LPA 2012 protocol with ATRA plus idarubicin and they have had a long event-free survival.
Assuntos
Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/genética , Translocação Genética/genética , Cromossomos , Proteínas de Fusão Oncogênica/genética , Cromossomos Humanos Par 17/genéticaRESUMO
Myelodysplastic syndromes (MDS) are a group of disorders of the hematopoietic stem cell. They are characterized by cytopenia(s), dysplasia of one or more cell lines, ineffective hematopoiesis, and an increased risk for developing acute myelogenous leukemia. The classification of MDS has been complicated due to the great heterogeneity in clinical phenotype as well as in the morphological and cytogenetic characteristics. The prognostic value of cytogenetic abnormalities in MDS has been analyzed in multicenter studies. This approach raised the development of the revised International Prognostic Scoring System (IPSS-R), which analyzes five prognostic variables, among which the cytogenetic study stands out. According to the cytogenetic findings, a classification of MDS in five subgroups was developed. Knowledge of the cytogenetic abnormalities has led to the study of genes involved in various chromosomal rearrangements. Moreover, DNA sequencing has helped to identify mutations in approximately 50 genes related to signal transduction, DNA methylation, transcriptional regulation, and RNA splicing. Therefore, the cytogenetic study should be used to improve the classification and therapeutic management of MDS. This approach will be an essential tool for the development of targeted therapy protocols.
Los síndromes mielodisplásicos (SMD) son un grupo de alteraciones que involucran a las células madre hematopoyéticas, caracterizadas por citopenia(s), displasia en una o más líneas celulares, hematopoyesis ineficaz y riesgo mayor para desarrollar leucemia aguda mieloblástica. Su clasificación es complicada debido a la heterogeneidad citogenética que condiciona un fenotipo morfológico y clínico también variable. El valor pronóstico de las alteraciones citogenéticas ha sido analizado en estudios multicéntricos y culminó con el desarrollo del Sistema Internacional Revisado de Puntaje Pronóstico (IPSS-R), que analiza cinco variables pronósticas, entre las que destaca el estudio citogenético. Este estudio ha identificado cinco categorías con valor pronóstico: muy bueno, bueno, intermedio, malo y muy malo. El conocimiento de tales alteraciones ha conducido al estudio de genes involucrados en los distintos arreglos cromosómicos, habiendo identificado mutaciones en cerca de 50 genes, mismos que están relacionados con la transducción de señales, la metilación del ácido desoxirribonucleico (ADN), la regulación de la transcripción y con el proceso de corte y empalme del ARN. Actualmente el estudio citogenético es el estándar de oro para el correcto estudio y clasificación de los SMD.
Assuntos
Aberrações Cromossômicas , Testes Genéticos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Marcadores Genéticos , Humanos , Mutação , Síndromes Mielodisplásicas/classificação , Prognóstico , Análise de Sequência de DNA , Translocação GenéticaRESUMO
OBJECTIVE: to show clinical and therapeutic findings in patients with diagnosis of acute megakaryoblastic leukemia (AML). METHODS: twenty four patients with diagnosis AML was carried out. Clinical, laboratory survey results and treatment response were studied. Nineteen patients had primary form and five secondary, attended during a period of eight years. The diagnosis was established by a highly clinical suspicious, with immunophenotype cytometry flow or/and bone biopsy with immunohistochemistry study which proves definitely AML. RESULTS: Fourteen were women, the median age was 43 years, 18 were treated with antineoplasic agents, ten obtained response, six complete and four partial. The response may improve with schemes with high dose of cytosine arabinoside. CONCLUSIONS: our results with the treatment showed that 27 % patients are alive under maintenance treatment long 18 months. The allogeneic bone marrow transplant seems to be one more option in long term.