Weidmann E, Brieger J, Bergmann L, Hoelzer D, Mitrou P S
Department of Internal Medicine, J.W. Goethe University, Frankfurt/M, Germany.
Leuk Res. 1995 Jul;19(7):469-76. doi: 10.1016/0145-2126(95)00012-d.
Preliminary clinical studies including interleukin 2 (IL-2) in chemotherapy strategies for treatment of acute myeloblastic leukemia (AML) suggest that IL-2 may improve the disease-free survival of the patients. Because of reports showing interleukin 2 receptor expression on AML blasts, it is important to know whether IL-2 may directly influence these leukemic cells. In initial studies using flow cytometry to analyze surface expression of interleukin 2 receptors (IL-2R), we found expression of the IL-2R alpha chain on blast cells in 26% and of the IL-2R beta-chain in 81% of the patients. To confirm these results at the transcriptional level, we studied the expression of RNA of the IL-2R alpha, beta, and gamma chains by RT-PCR in the bone marrow of 38 newly diagnosed patients with AML and in three AML-derived cell lines. RNA of the alpha chain was detectable in 11/38 patients, the beta chain in 10/38 patients and the gamma chain in 30/38 patients with AML. Blast cells obtained from colonies growing in semisolid media expressed mRNA for IL-2R. RNA for all three IL-2R chains was expressed in lines KG1, HEL 92.1.7 and K562. In comparison with unstimulated cell lines, incubation of the three lines with various amounts of IL-2 over 3 and 14 days did not increase their growth or change message expression of IL-2R, IL-10, and TGF-beta and surface expression of the adhesion molecules CD 11, CD 18, CD 29 and CD 54. In conclusion, despite expression of IL-2 receptors, AML blasts do not respond to IL-2 by proliferation, message expression for various cytokine genes and surface expression of cellular adhesion molecules.
包括白细胞介素2(IL-2)用于急性髓细胞白血病(AML)化疗策略的初步临床研究表明,IL-2可能会改善患者的无病生存期。由于有报道显示AML原始细胞上存在白细胞介素2受体表达,因此了解IL-2是否可能直接影响这些白血病细胞很重要。在最初使用流式细胞术分析白细胞介素2受体(IL-2R)表面表达的研究中,我们发现26%的患者原始细胞上有IL-2Rα链表达,81%的患者有IL-2Rβ链表达。为了在转录水平证实这些结果,我们通过逆转录聚合酶链反应(RT-PCR)研究了38例新诊断的AML患者骨髓以及三种AML来源细胞系中IL-2Rα、β和γ链的RNA表达。在38例AML患者中,11例可检测到α链RNA,10例可检测到β链RNA,30例可检测到γ链RNA。从半固体培养基中生长的集落获得的原始细胞表达IL-2R的mRNA。三种IL-2R链的RNA在KG1、HEL 92.1.7和K562细胞系中均有表达。与未刺激的细胞系相比,这三种细胞系在3天和14天内用不同剂量的IL-2孵育后,其生长未增加,IL-2R、IL-10和转化生长因子β(TGF-β)的信息表达以及黏附分子CD 11、CD 18、CD 29和CD 54的表面表达均未改变。总之,尽管存在IL-2受体表达,但AML原始细胞对IL-2的增殖、各种细胞因子基因的信息表达以及细胞黏附分子的表面表达均无反应。