|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1993 : ¥1,000,000 (Direct Cost : ¥1,000,000)
In the present research project, the investigator has been found that G-CSF induced AML cells to progress into the first stage (primary granule expression) of granulocyte differentiation. Of importance, this was almost always accompaniedby the expression or augmentation of CD95 (Fas), which was able to conduct Fas-mediatedapoptotic signal. Later in the second fiscal year (1994), we established a novel AML cell line, KB-8, which found to share many characteristics of those of primary AML cells. Using this cell line, the investigator was able to recapitulate our previous findings obtained by primary AML cells. Moreover, KB-8 cell line enabled us to conduct more precise investigation into biological effects of G-CSF on AML cells. Following data were obtained ;
(1) rhG-CSF does not induce final maturation of AML cells. However, it does drive AML cells to progress into the first stage of granulocyte differentiation ; i.e., primary (azur) granule expression, expression/augmentation of CD11b, CD13, CD14 and CD33 differentiation-associated molecules, as well as CD95 (Fas) apoptotic signal receptor.
(2) The CD95 (Fas) molecules thus induced by rhG-CSF,conducted apoptotic signal generated by the binding of a specific anti-Fas IgM-type antibody (clone CH11).
(3) Since KB-8 cells constitutively expressed Bcl-2 anti-apoptosis protein, the investigator expected to find an inverse-relationship between CD95 and Bcl-2 expression. By this point, however, Bcl-2 protein expression did not alter significantly by the addition of rhG-CSF.
In summary, rhG-CSF could induce AML cells to differentiate into the first stage of granulocyte maturation pathway. This is accompanied by the expression of CD95 (Fas) which can conduct a Fas-mediatedapoptotic signal. These results may raise the intriguting possibility that rhG-CSF prompt AML cells susceptible to Fas-mediated apoptosis. If this is the case, rhG-CSF may has a novel therapeutic impact in treatment of patients with AML.