新维甲类联合γ干扰素对急性单核细胞白血病细胞增殖分化作用的体外研究

In vitro study on the effects of the novel retinoids combined with IFN γ on the proliferation and differentiation of fresh acute monocytic leukemic cells

目的探讨新研制的维甲类查尔酮酸Ｒ９１５８和ＹＳ９０４０１２联合γ干扰素（ＩＦＮγ）在急性单核细胞白血病分化疗法中的应用价值。方法应用细胞形态学、四氮唑蓝（ＮＢＴ）还原反应和非特异酯酶乙酸萘酚（ＤＣＥ）、细胞分化免疫表型ＣＤ１４和ＣＤ６８、ＣＦＵＬ集落形成抑制率等变化，体外研究其对６例急性单核细胞白血病患者白血病细胞的增殖分化作用。结果经ＹＳ９０４０１２联合ＩＦＮγ处理后，单核细胞由原始阶段变成较成熟的单核细胞，ＮＢＴ还原反应阳性率和ＤＣＥ分别由２３．４％和２５０％上升到６１．５％和５２．０％，ＣＤ１４和ＣＤ６８表达增强，ＣＦＵＬ集落增殖明显受抑。通过比较，ＹＳ９０４０１２联合ＩＦＮγ诱导细胞分化和抑制集落形成活性优于Ｒ９１５８和全反式维甲酸联合用药组（Ｐ＜０．０１）。结论ＹＳ９０４０１２联合ＩＦＮγ诱导分化治疗单核细胞白血病可能有一定临床实用价值。

Objective To investigate the prospect for clinical use of novel retinoids YS 904012 and R9158 in combination with IFN γ in inducing differentiation of acute monocytic leukemia.Methods The effects of novel retinoids with IFN γ on the differentiation and clonal proliferation of fresh leukemia cell from 6 monocytic leukemia patients were studied in vitro. Cell morphological examination,nitro tetrazolium blue reduction test and DCE, expression of CD 14 and CD 68 and CFU L were used in the study. Results The primary leukemia cell,cultured with the combination of YS 904012 and IFN γ,became more mature in morphology.The NBT reduction rate and DCE were increased from 23.4% and 25.0% to 61.5% and 52.0%, respectively. The expression of CD 14 and CD 68 was increased.The growth of the leukemic colony in semi solid culture was markedly inhibited. The activity of YS 904012 combined with IFN γ in inhibiting proliferation and inducing differentiation of monoblast was greater than that of R9158 or all trans retinoic acid in combination with IFN γ(P<0.01).Conclusion The YS 904012 combined with IFN γ is worthy of further study for clinical differentiation therapy of acute monocytic leukemia.