1、FROM Phospholipid Scramblase 1 (PLSCR1) TO Leukemic Cell Differentiation 从磷脂酰爬行酶到白血病细胞分化,Health Science Center，SIBS Zhao Ke-Wen,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,造血干细胞,成熟血细胞,白血病 （Leukemia）,Specific translocation t(15;17),急性早幼粒细胞性白血病（APL）,As2O3,APL is curable,Differentiation Therapy,Cancer Targ
2、et Therapy,cholinephospholipids : sphingomyelin ;phosphatidylcholine PC aminophospholipids : phosphatidylserine PS ; phosphatidylethanolaminePE,ZHAO KW et al BLOOD2004,Normal hemostasis but defective hematopoietic response in plscr1-/-mice ;MmTRA1a, a truncated form of murine PLSCR1 was identified i
3、n a monocytic leukemia cell line,In mice,In human,AML patients with higher levels of PLSCR1 mRNA were associated with significantly longer overall survival, particularly in patients of the AML-M4 subtype,PLSCR1,Leukemic Cell differentiation,?,ATRA could dose- and time-dependently induce the expressi
4、on of PLSCR1 (protein level, in NB4 cells),ATRA could time- and dose-dependently induce the expression of PLSCR1 (mRNA level, in NB4 cells),ATRA,PLSCR1,NB4,ATRA could not induce PLSCR1 expression in ATRA-resistant NB4-derived NB4-LR1 cells,PLSCR1,a,2 1 0 0 1 2 3 4 days,4 2 0,1007550250,CD11b+ cells%
5、,G3PDH,c,b,PLSCR1 /G3PDH,PLSCR1,-actin,NB4,NB4-LR1,0 1 2 3 4 days,0 1 2 3 4 days,ATRA,PLSCR1,NB4,LR1,PLSCR1,PLSCR1,Granulocyticdifferentiation,?,ATRA,Increase in PLSCR1 expression is not limited to ATRA-induced granulocytic differentiation,PLSCR1,Granulocyticdifferentiation,ATRA,?,PLSCR1,?,ATRA,DMSO
6、:dimethyl sulfoxide SB: sodium butyratea histone deacetylase inhibitor PMA: phorbol 12-myristate 13-acetate VD3:Vitamin D3,C: PLSCR1 expression induced by ATRA and PMA was not restricted to leukemic cells,PLSCR1,?,ATRA,PMA,PLSCR1,Leukemic cell differentiation,?,1,2,PLSCR1,ATRA,PMA,PKC,?,What is PKC?
7、,cPKC (conventional PKC),nPKC (novel PKC),aPKC (Atypical PKC),phorbol esters,Ca2+,phorbol esters,Ca2+,phorbol esters,Ca2+,phorbol esters,Ca2+,a,b,PKC phosphorylation/activation is accompanied by increased PLSCR1 expression,Rottlerin: a PKC-specific inhibitor,Ectopic expression of the catalytic fragm
8、ent of PKC (CF ) can induce expression of PLSCR1,CON CF1.5,1 0.5 0,B,PLSCR1,-actin,CON N1 CF1.0 CF1.5,CF : catalytic fragment of PKC ,G3PDH,PLSCR1,A,Conclusion1: PLSCR1 can be up-regulatedby activation of PKC,PLSCR1,Leukemic cell differentiation,?,Inhibition of PLSCR1 expression by siRNA partially b
9、locks ATRA- and PMA-induced differentiation,c: control p: PMA r: ATRA,Conclusion2: PLSCR1 involves in leukemic cell differentiation,2004-4-28 submission to BLOOD2004-5-26 BLOOD response : I am happy to report that the paper was favorably received and, provided an appropriate revision is prepared, ca
10、n be accepted for publication in Blood. interesting, convincing ,(Blood. 2004;104:3731-3738),BLOOD, 1 DECEMBER 2004 VOLUME 104, NUMBER 12,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,SIBS, AC Guo-Qiang Chen; Qian Zhao; Xi Li; Dong Li; Ying Huang; Ci-Xiang Zhou; Jing Zhang; Zhen-Gang Peng; Shi-Hua Liao Mei-Yi Zhou; Meng Zhao,THANKS!,
