[Effect of Daunorubicin on Release and Procoagulant Activity of Microparticles Derived from Acute Promyelocytic Leukemia Cells].

OBJECTIVE: To investigate the effect of daunorubicin on the number and procoagulant activity of Microparticles derived from acute promyelocytic leukemia(APL) cells. METHODS: APL cells were isolated from bone Marrow of 5 newly diagnosed APL patients, the bone marrow mononuclear cells were collected from 5 patients with iron deficiency anemia as control.APL cells were treated with different concentration of daunorubicin(0.1,0.5,1.0 and 2.0µmol/L) for 24 h. Microparticles were extracted from the cell culture medium for qualitative anaysis of the extracted microparticles.The morphologic features of the microparticles were observed by transmission electron microscopy.The number of microparticles was detected by flow cytometry.The procoagulant activity of microparticles was measured by recalcification time assays. RESULTS: Under a transmission electron microscope, theextracted microparticles took a round or oval morphology with a transparent center,and their diameters were arund 100nm, consistent with the morphological characteristics of microparticles. Compared with bone marrow mononuclear cells-derived microparticles,the counts of the bone marrow APL cells-derived microparticles significantly increased(P<0.05).Daunorubicin increased the shedding of microparticles in a dose-dependent manner(r=0.73,P<0.01).Compared with normal bone marrow mononuclear cells-derived microparticles,bone marrow APL cells-derived microparticles showed higher procoagulant activity(P<0.05).Daunorubicin treatment enhanced the prccoagulant activity of APL cells-derived microparticles which paralleled the increasing drug concentrations(r=-0.78,P<0.01). CONCLUSION: Daunorubicin can promote the release of APL cells-derived microparticles and enhance their related procoagulan activity.

[Experimental advance of targeted medicines for chronic myeloid leukemia--review].

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder from hematopoietic stem cell disorder characterized by the consecutive expression of bcr-abl gene, and the translation product of which has enhanced tyrosine kinase activity and can activate a series of downstream signal transduction proteins and results in the occurence of CML. Although the application of imatinib (IM) makes nearly all patients with CML in chronic phase achieve a complete hematologic remission, and 90%of those treated in the early chronic phase achieve a complete cytogenetic remission, but the development of resistance to IM in the course of treatment and even in the beginning of the treatment forced people to develop new agents and to combine the new agents with IM in order to achieve better therapeutic result. This article reviews the experimental advances of targeted therapeutics in CML recent years.