RESUMO
Treatment of children with acute lymphoblastic leukemia (ALL) is based on P-glycoprotein (P-gp)-dependent cytostatics. We assessed the P-gp function in blast cells as a possible prognostic factor and its influence on the overall survival. P-gp function was measured using the verapamil-sensitive Rhodamine efflux. Cell samples from 7 of 45 (16%) patients revealed rhodamine-efflux positive blasts. There were no relations between the presence of P-gp, clinical characteristics (age, sex, hepatomegaly, and splenomegaly) and initial laboratory parameters (immunophenotype, white blood cells count, and serum lactate dehydrogenase) in ALL. P-gp activity plays a negative role, both for a remission achieved on day 33 and for susceptibility to steroid therapy. Children bearing rhodamine-efflux positive blasts had a significantly shorter 5-year overall survival of 35%, as compared with 74% in those negative for P-gp function. Lack of any association with clinical characteristic and initial laboratory parameters suggests that presence of P-gp is an independent prognostic factor.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Citometria de Fluxo , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Fatores de Risco , Fatores Sexuais , Resultado do TratamentoRESUMO
In this case study authors presented the clinical characteristics of X-linked agammaglobulinemia (XLA) associated with agranulocytosis diagnosed in a 2-year-old boy. Affected child lacked circulating mature B cells, presented low levels of serum immunoglobulins, but did not suffer from recurrent bacterial infections. XLA is a primary immunodeficiency caused by a defective tyrosine kinase (Btk) in B cells. Our patient and his mother have a mutation in the BTK gene, described as W281X. During therapy with intravenous gammaglobulin, the boy has not experienced agranulocytosis. It is important to consider a primary immunodeficiency diagnosis when a child presents agranulocytosis or neutropenia and a recurrent infectious disease.
Assuntos
Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Agranulocitose/etiologia , Cromossomos Humanos X , Ligação Genética , Proteínas Tirosina Quinases/genética , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/complicações , Agamaglobulinemia/terapia , Agranulocitose/diagnóstico , Pré-Escolar , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Mutação , Fatores de Tempo , Resultado do TratamentoRESUMO
A family of phenotypically and biologically different transplantable hamster melanomas was derived from a single tumor more than 40 yr ago. In this work, we were seeking the differences between the abilities of the cells from two biologically heterogeneous (melanotic and amelanotic) members of this family to undergo spontaneous or camptothecin-induced apoptosis. We studied these differences by looking at three important features of the apoptotic process, i.e. binding of annexin V, DNA fragmentation and caspase-3 activity. Of these, annexin binding and DNA fragmentation were more pronounced in the parental, melanotic line while the activity of caspase-3 was stronger in the amelanotic tumor cells. We concluded that a spontaneous alteration of the original, melanotic melanoma line into an amelanotic one, associated with more aggressive tumor progression, was accompanied by significant decrease in ability to undergo spontaneous and camptothecin-induced apoptosis, and that apoptosis of these two cell types may not depend on the activity of caspase-3.
