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Study Of ATRA And Arsenic Trioxide On Acute Promyelocytic Leukemia Cells In Vitro And In Vivo

Posted on:2007-09-23Degree:MasterType:Thesis
Country:ChinaCandidate:K H BiFull Text:PDF
GTID:2144360185985530Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Objective: Both all trans retinoic acid(ATRA)and arsenic trioxide was effective in treatment of APL, but with the widespread use of ATRA and arsenic trioxide in clinics, the hyperleukocytosis was often observed in some of them. In view of the close relationship between cytokines and differentiation or proliferation of normal hematopoietic cells or leukemia cells, we detected the variation of some important serum cytokines to detect the mechanism of leukocytosis or hyperleukocytosis.Methods: Diagnoses of APL were performed according to the FAB cytological classification criteria and cytogenetic criteria. Primary APL cells were separated and purified by traditional Ficoll-Hypaque density centrifugation and enriched after adherence to plastic surfaces .IL-1β ,IL-6,IL-8,TNF α and G-CSF levels in the supematants of cultured leukemia cell were estimated by ELISA method. NBT method was used to detect the differentiation of APL cells at the same time as evaluating hematopoietic growth factors. Results: APL cells showed a significant increase of IL-1β and G-CSF secretion,and a significant decrease of IL-6 and IL-8,however, there was no obvious variation of TNF α ,if compared with that of APL cells without exposure to ATRA. On the other hand, the proliferation ratio of APL cells in vitro was statistically correlated to the IL-1β secretion ratio or G-CSF secretion ratio. In the aspect of arsenic trioxide induction of primary APL cells, APL cells showed the similar tendency of cytokine secretion to ATRA induction.The serum level of either sICAM-1 or sVCAM-1 was up-regulated after treatment with ATRA.The results of FACS also indicated that cell surface sICAMl,CD11b and CD106 also obviously up-regulated during the induction of ATRA. Conclusion: Augmentation of serum IL-1β and G-CSF,together with high level of their secretion after exposure to ATRA or As2O3plays important role inleukocytosis,and the leukocytosis maybe partly due to the up regulation of adhesive molecules.
Keywords/Search Tags:acute promyelocytic leukemia, differentiation, leukocytosis, cytokine, Myc family, adhesive molecule
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