ABSTRACT
In the present study, we analyzed AURKA and AURKB gene expression in 70 acute myeloid leukemia (AML) patients. There was no difference between leukemic samples and bone marrow mononuclear cells (BMMCs, n = 8) or CD34(+) progenitors (n = 10) from healthy donors. High white blood cells (WBC) counts were observed in the AURKA(+) and AURKB(+) groups, but no significant differences regarding age, gender, platelet counts or frequency of FLT3-ITD mutations. AURKA, but not AURKB, expression was independently associated with high WBC counts (OR: 3.15, 95%CI 1.07-9.24, p = 0.03). Moreover, the majority of cases that overexpressed AURKA and AURKB presented unfavorable cytogenetic abnormalities (p < 0.001). In conclusion, we described a significant association between overexpression of AURKA/B and cytogenetics findings in AML, which may be relevant to new therapeutic approaches, based on Aurora kinase inhibitors.
Subject(s)
Chromosome Aberrations , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Protein Serine-Threonine Kinases/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Aurora Kinase A , Aurora Kinase B , Aurora Kinases , Child , Child, Preschool , Female , Gene Expression Profiling , Humans , In Situ Hybridization, Fluorescence , Leukemia, Myeloid, Acute/metabolism , Leukocyte Count , Male , Middle Aged , Mutation , Protein Serine-Threonine Kinases/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Young Adult , fms-Like Tyrosine Kinase 3ABSTRACT
CONTEXT AND OBJECTIVE: Aplastic anemia and agranulocytosis are rare but life-threatening disorders, often caused by drugs and other environmental exposures. Reported incidence of these diseases seems to vary between different geographic regions, and few data on their incidence are available for Latin American countries. The aim of this work is to determine the incidence of agranulocytosis and aplastic anemia in Brazil. DESIGN AND SETTING: Incidence study. Seven centers took part in the pilot phase, so as to represent all Brazilian regions. METHODS: Each center conducted an active search for new cases in a defined region by means of regular contacts with all hematologists, main clinical laboratories and clinicians in hospitals of the region. RESULTS: 74 patients with aplastic anemia and 16 with agranulocytosis were identified. Patients with agranulocytosis had a median age of 31 years (interquartile range, IQR: 12.5-48.2); 32.2% were male and 81.2% were white. The median age of aplastic anemia patients was 21 years (IQR 15.0-35.2); 62.2% were male, 50.0% were white and 39.2% mulatto. The incidence of agranulocytosis was estimated to be 0.5 cases per million individuals per year, ranging from 0.0 to 1.1 cases per million per year between regions. The incidence of aplastic anemia was 2.7 cases per million per year, ranging from 1.1 to 7.1 cases per million per year between regions. CONCLUSIONS: Aplastic anemia and agranulocytosis are rare diseases in Brazil. However, there is considerable variability in their incidences between different regions.
Subject(s)
Agranulocytosis/epidemiology , Anemia, Aplastic/epidemiology , Adult , Brazil/epidemiology , Female , Humans , Incidence , Male , Pilot ProjectsABSTRACT
CONTEXTO E OBJETIVO: A anemia aplástica e a agranulocitose são doenças raras, entretanto freqüentemente letais. Muitas vezes são causadas por medicações e outras exposições ambientais. A incidência dessas doenças parece variar consideravelmente entre diferentes regiões geográficas, e poucos dados sobre a incidência são disponíveis para os países da América Latina. O objetivo deste trabalho é determinar a incidência de anemia aplástica e agranulocitose no Brasil. TIPO DE ESTUDO E LOCAL: Estudo de incidência. Sete centros participaram da fase piloto do estudo representando as cinco regiões brasileiras. MÉTODOS: Cada centro realizou busca ativa por novos casos em uma região definida, por meio de contatos regulares com todos os hematologistas, principais laboratórios clínicos e clínicos de hospitais de sua região. RESULTADOS: Foram identificados 74 casos de anemia aplástica e 16 casos de agranulocitose. A mediana de idade dos pacientes com agranulocitose foi de 31 anos (intervalo inter-quartil IIQ 12,5 48,2), 32,2% eram do sexo masculino e 81,2% eram da raça branca. A mediana de idade dos pacientes com anemia aplástica foi de 21 anos (IIQ 15,0-35,2), 62,2% eram do sexo masculino, 50,0% da raça branca e 39,2% da raça parda. A incidência de agranulocitose foi estimada em 0,5 casos/milhão de habitantes/ano, variando de 0,0 a 1,1 caso/milhão de habitantes/ano entre as diferentes regiões brasileiras. A incidência de anemia aplástica foi de 2,7 casos/milhão de habitantes/ano, variando de 1,1 a 7,1 casos/milhão de habitantes/ano entre as diferentes regiões. CONCLUSÕES: A anemia aplástica e a agranulocitose são doenças raras no Brasil. Entretanto existe considerável variabilidade na incidência destas doenças entre as diferentes regiões brasileiras.
Subject(s)
Humans , Male , Female , Agranulocytosis/epidemiology , Anemia, Aplastic/epidemiology , Brazil/epidemiology , Incidence , Pilot ProjectsABSTRACT
E descrito um metodo quimiluminescente simples e sensivel para a caracterizaçao da mieloperoxidase intracelular, utilizavel para a diferenciaçao entre blastos comprometidos com a linhagem mieloide e linfoide de paciente com leucemia aguda. Estabelecendo-se o ponto de "cut-off" em 13 mV de quimiluminescencia, todos os casos de leucemia mieloide aguda puderam ser diferenciados dos casos de leucemia linfoide aguda. A tecnica proposta demontrou a atividade peroxidasica inclusive em blastos do tipo MO e M7 (classificaçao FAB) os quais usualmente nao se coram nas preparaçoes citoquimicas classicas e requerem estudos com microscopia eletronica para a detecçao da mieloperoxidade
