Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology
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Zhongguo Shi Yan Xue Ye Xue Za Zhi · Dec 2005
[A preliminary study on mechanisms for resistance of CML patient BM-derived bcr/abl+ and Flk1+CD31-CD34- stem cells to STI571 in vitro].
To evaluate the effect of imatinib mesylate (STI571) on primitive/committed malignant progenitor cells in chronic myelogenous leukemia (CML) and to further elucidate the mechanisms involved in CML relapse and in some CML cells resistant to STI571, bone marrow-derived malignant bcr/abl-positive, Flk1(+)CD31CD34(-) cells with hemangioblastic characteristics from CML patients were grown in Methocult GF+ media with or without STI571, and inhibitory effect of STI571 on proliferation of differentiated and differentiating, bcr/abl(+), Flk1(+)CD31CD34(-) cells with hemangioblastic characteristics was investigated in vitro. The results showed that in vitro exposure to 5 micromol/L STI571 (the concentration of STI571 usually achieved in patients is 1-2 micromol/L) for 96 hours inhibited bcr/abl(+) committed progenitors (colony-forming cells, CFCs). ⋯ It is concluded that CML primitive stem cells remain viable in the presence of STI571 and that inhibition of bcr/abl tyrosine kinase by STI571 restores normal hematopoiesis by removing the proliferative advantage of CML committed progenitors but that elimination of all CML progenitors may not occur. So despite dramatic short-term responses in vivo, such in vitro resistance to STI571, may translate into disease relapse after prolonged therapy.
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Zhongguo Shi Yan Xue Ye Xue Za Zhi · Apr 2005
[Influence of repeated platelet donation on megakaryopoiesis in donors].
To explore influence of platelet donation on donor's megakaryocytopoiesis, platelet counts and plasma concentrations of thrombopoietin (TPO), interleukin-3 (IL-3), IL-6 and nitric oxide (NO) were determined in 42 frequent platelet donors (undergoing plateletpheresis more than once a month for 24 months and their mean platelet yield of collection was 2.5 x 10(11)), in 62 limited platelet donors (undergoing plateletpheresis less than once a month for 24 months) after a donation-free period of > 5 weeks and in 40 whole blood donors who never undergoing plateletpheresis after a donation-free period of > 6 months. The results showed that the TPO levels was significantly lower in frequent platelet donors than in limited platelet donors (P < 0.01) and whole blood donors (P < 0.01). There were no significant differences between three groups in platelet counts, IL-3, IL-6 and NO. These findings suggest that the number of megakarocytes significantly increased in frequent platelet donors.
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Zhongguo Shi Yan Xue Ye Xue Za Zhi · Aug 2002
Allogeneic bone marrow transplantation for chronic myeloid leukemia using HLA identical sibling donors primed with G-CSF.
Many studies have shown that G-CSF mobilized peripheral blood progenitor cell transplants (PBPCT) manifests faster recovery kinetics than conventional bone marrow transplants. This potential advantage of PBPCT still needs to be balanced against the risk of acute and chronic GVHD associating with the infusion of 10 - 15 fold higher donor lymphocyte number in unmanipulated allogeneic PBPCT than the marrow graft. To evaluate the effect of G-CSF primed bone marrow as a source of stem cells in the HLA-matched sibling transplantation, G-CSF primed with non-primed donor marrow in engraftment and incidence of GVHD for a homogenous group of patients with chronic myeloid leukemia (CML) were compared. ⋯ There were not significant differences in the incidence of the chronic GVHD (24% vs 33.3%), relapse rate (12.5% vs 11.1%) and overall survival rate (78.1% vs 66.7%, P = 0.32) during 6 - 50 months of follow-up. In conclusion, G-CSF primed donor marrow accelerates engraftment. Although G-CSF did not change the total CD3(+) cells in bone marrow, it altered the ratio of CD4(+) and CD8(+) cells and significantly reduced the incidence of acute GVHD.