(精编)【医学课件】 从磷脂酰爬行酶到白血病细胞分化教学课件.pptVIP

第一作者论坛 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） 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 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 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 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 0 100 75 50 25 0 CD11b+ cells% 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 Granulocytic differentiation ? ATRA Increase in PLSCR1 expression is not limited to ATRA-induced granulocytic differentiation PLSCR1 Granulocytic differentiation ATRA ? PLSCR1 ? ATRA DMSO:dimethyl sulfoxide SB: sodium butyrate a 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 PKCδ ? What is PKC?? cPKC (conventional PKC) nPKC (novel PKC) aPKC (Atypical PKC) phorbol esters Ca2+ phorbol esters Ca2+ phorbol esters Ca2+ phorbol esters Ca2+ a b ? ? ? ? ? ? ? ? 第一作者论坛