ABSTRACT
Objective To explore the influence of mitochondrial permeability transition pore opening and cytochrome C (Cyt C) being discharged on the apoptotic mechanism of HL-60 cell induced by desferrioxamine (DFO),so as to provide scientific basis for the clinicians to adopt the strategy of iron deprivation to treat human leukemia.Methods HL-60 cells were co-cultivated with various concentration of DFO for 24-72 hours,then the apoptotic cells and the changes of mitochondrial membrane potential(△Ψm) were examined by means of flow cytometry(FCM),and Cyt C in cytoplasm was detected by way of celluar immunohistochemistry.Results The cell apoptotic rate assumed rising tendency as the highest rate could be up to (44.10 ± 6.3 1) ％,and the effect was of time-and-dose dependence (P ＜0.01).FCM could detect the △Ψm declining(P ＜ 0.05),and the Cyt C positive cell rate was higher than the controls,the differences were of statistical significance(P ＜ 0.05).Conclusions DFO can induce the HL-60 cells apoptosis,and the possible mechanism is that DFO make the mitochondrial permeability transition pore open and get Cyt C discharged from the mitochondria.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical features, diagnosis and treatment of pediatric myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>Twenty-eight children with MDS between January 2006 and March 2012 were enrolled in the study. Clinical symptoms, signs, laboratory examinations, treatment and outcomes were retrospectively studied.</p><p><b>RESULTS</b>Anemia (96%), bleeding (68%), fever (68%) and hepatosplenomegaly (61%) were main clinical manifestaions in the 28 patients. Three cases (11%) converted into acute monocytic leukemia (M5), erythroleukemia (M6) or acute megakaryocytic leukemia (M7) one to two months later. Bone marrow proliferation mainly demonstrated as active or obviously active. One or two lineages of hematopoietic dysplasia were mostly observed in all 28 cases and obvious iron metabolism disorders were found in these patients. Cytogenetic abnormalities were detected in 45% of the 28 cases, most of which were numeral chromosome abnormalities. T cell, B cell and NK cell numbers decreased, Th cell numbers decreased, Ts cell numbers increased and Th /Ts inversed. Eight cases gave up treatment when confirmed. Of the 8 cases receiving symptomatic and supportive treatment alone, one was lost, one showed disease stability, and the remaining 6 cases showed disease progression. One patient who underwent induced differentiation and one who received hematopoietic therapy showed disease progression. Ten patients underwent chemotherapy. Two cases had no bone marrow remission after single agent chemotherapy. Of the 8 cases who underwent multi-drug combination chemotherapy, 4 cases achieved partial or complete remission of bone marrow.</p><p><b>CONCLUSIONS</b>Pediatric MDS is characterized by a lack of typical clinical manifestations, and a high rate of conversion to leukemia. Bone marrow proliferation is mainly active in children with MDS. One or two lineages of hematopoietic dysplasia is common. Among the cytogenetic abnormalities, numeral chromosome abnormalities are common. Obvious iron metabolism disorders and abnormal cellular immunity are found in children with MDS. Multi-drug combination chemotherapy appears to slow the course of the disease.</p>