Analysis of Signals Leading to Differentiation of Immature HL-60 after Administration of IL-4

[摘要] Treatment of acute myeloid leukaemia (AML) cells withdifferentiation agents leads not only to the acquisition of normalphenotypes but also contributes to the understanding of specialimmuno-haematology issues. For instance, induction of HLA-DRantigens on human promyelocytic leukaemia HL-60 cells byinterleukin-4 (IL-4) is of pivotal importance in immunology notonly because class II expression is prerequisite to antigenrecognition and response but also because IL-4 participates in aplethora of inflammatory or non-inflammatory reactions. At the sametime, the same observation coupled with an increase in Mac-1, maturemonocyte marker, is revealing ways to haematologists for convertingmalignant cases to normal situations. Based on previous reports thatHLA-DR induction by IL-4 in the HL-60 system is mediated via theG-protein system (p21ras), this study was undertaken in order todefine the intermediate signalling steps followed by this agent fromthe moment it is added to cultures to the differentiated cellularform obtained. It is proposed that IL-4 increasesp21raswhich in turnsuppresses the HL-60 cells'p34cdc2constitutive expression. Thisinhibition appears to be responsible for the subsequently.observedcessation ofgrowth. Concomitant to decreased cellular proliferation,HI-DR antigen expression increases, a finding that matches theinitially mentioned induction ofp21rassince its inhibition abolishes HI-DR upregulation.

[学科分类] 生理学与病理学