从磷脂酰爬行酶到白血病细胞分化课件.ppt

FROM Phospholipid Scramblase 1 (PLSCR1) TO Leukemic Cell Differentiation从磷脂酰爬行酶到白血病细胞分化;恶性肿瘤是威胁人类健康的主要杀手。 在我国，白血病占恶性肿瘤的第7位 ;细胞分化;白血病 （Leukemia）;Specific translocation t(15;17);Acute promyelocytic Leukemia (APL);cholinephospholipids : sphingomyelin ;phosphatidylcholine [PC] aminophospholipids : phosphatidylserine [PS] ; phosphatidylethanolamine[PE] ;;;ZHAO KW et al BLOOD2004;Normal hemostasis but defective hematopoietic response in plscr1-/-mice ; MmTRA1a, a truncated form of murine PLSCR1 was identified in a monocytic leukemia cell line;;;In human;PLSCR1;ATRA could dose- and time-dependently induce the expression of PLSCR1 (protein level, in NB4 cells);ATRA could time- and dose-dependently induce the expression of PLSCR1 (mRNA level, in NB4 cells);ATRA;ATRA could not induce PLSCR1 expression in ATRA-resistant NB4-derived NB4-LR1 cells;ATRA;PLSCR1;Increase in PLSCR1 expression is not limited to ATRA-induced granulocytic differentiation;PLSCR1;PLSCR1;DMSO:dimethyl sulfoxide SB: sodium butyrate a histone deacetylase inhibitor PMA: phorbol 12-myristate 13-acetate VD3:Vitamin D3;PLSCR1;;PLSCR1;What is PKC??;PKC ? phosphorylation/activation is accompanied by increased PLSCR1 expression;Ectopic expression of the catalytic fragment of PKC ?(CF ?) can induce expression of PLSCR1;Conclusion1:PLSCR1 can be up-regulated by activation of PKC?;PLSCR1;Inhibition of PLSCR1 expression by siRNA partially blocks ATRA- and PMA-induced differentiation;Conclusion2: PLSCR1 involves in leukemic cell differentiation;2004-4-28 submission to BLOOD 2004-5-26 BLOOD response : ‘I am happy to report that the paper was favorably received and,provided an appropriate revision is prepared, can be acceptedfor publication in Blood.’ ‘interesting, convincing ‘;(Blood. 2004;104:3731-3738);TO Share with you;团队精神 充分的准备 主动地交流 实干+巧干 规范实验 +归纳总结 正确地对待挫折和失败 ;acknowledgements;THANKS!