Hassan H, Zander A
Oncol Rep. 1997 Nov-Dec;4(6):1141-9. doi: 10.3892/or.4.6.1141.
In acute myeloid leukaemia (AML), age has a definite effect on the biology of the disease and also determines the outcome of chemotherapy. AML cells constitutively express mRNA and produce several haematopoietic cytokines. The haematopoietic cytokines: SCF, IL-3, GM-CSF and G-CSF induce leukaemic colonies or activate DNA synthesis in about 80% of AML cases. Both M-CSF and thrombopoietin stimulated AML cell proliferation is seen in vitro in about 50% of cases. Both IL-6 and IL-11 showed little proliferative activity on primary AML cells. The combinations of these cytokines were synergistic in stimulating the proliferation of AML cells. On the other hand, the inhibitory haematopoietic cytokines: TNF-alpha, TGF-beta, IFN-gamma and IL-4 have shown multiple effects on AML blast cell proliferation. In several in vitro systems, haematopoietic cytokines have failed to induce maturation of AML blasts. Only in AML with t(8;21), G-CSF has induced granulocytic maturation of AML blasts in vitro. AML cells with chromosomal abnormalities involving the 21q22 region differentiate in vitro into eosinophils in the presence of IL-5. IL-6 and IFN-alpha have induced megakaryocytic differentiation of blast cells from acute megakaryoblastic leukemia (M7) patients. The haematopoietic cytokines: SCF, IL-3 and GMCSF have protected in vitro AML cells from chemotherapy-induced apoptosis. Many clinical studies have been recently reported evaluating the effect of the haematopoietic cytokines: GM-CSF, G-CSF, IL-3 and PIXY321 as adjuncts to the chemotherapy of AML patients. Most studies have shown these haematopoietic cytokines to be well-tolerated and effective in augmenting neutrophil recovery in elderly AML patients when given after chemotherapy. On the other hand, considerable number of studies using these cytokines before and during chemotherapy to recruit AML cells into cell cycle and thus make them more susceptible to chemotherapy have reaveled no benefit. Several clinical trials have shown promising results after the use of IL-2 either as remission induction therapy in refractory and/or relapsed AML patients or as post-remission consolidative immunotherapy. Haematopoietic cytokines administered after chemotherapy can shorten the duration of neutropenia and hospitalisation without a significant effect on treatment outcome. On the other hand, their use before and during chemotherapy has yielded no benefit, and instead have led to delay of platelet recovery and worse survival rate in some elderly AML patients.
在急性髓系白血病（AML）中，年龄对疾病生物学特性有明确影响，也决定化疗结果。AML细胞组成性表达mRNA并产生多种造血细胞因子。造血细胞因子：干细胞因子（SCF）、白细胞介素-3（IL-3）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）在约80%的AML病例中可诱导白血病集落或激活DNA合成。在约50%的病例中，体外可见巨噬细胞集落刺激因子（M-CSF）和血小板生成素均刺激AML细胞增殖。白细胞介素-6（IL-6）和白细胞介素-11对原代AML细胞几乎无增殖活性。这些细胞因子的组合在刺激AML细胞增殖方面具有协同作用。另一方面，抑制性造血细胞因子：肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）、干扰素-γ（IFN-γ）和白细胞介素-4对AML原始细胞增殖显示出多种作用。在多个体外系统中，造血细胞因子未能诱导AML原始细胞成熟。仅在伴有t(8;21)的AML中，G-CSF在体外可诱导AML原始细胞粒细胞成熟。存在涉及21q22区域染色体异常的AML细胞在白细胞介素-5存在下体外可分化为嗜酸性粒细胞。白细胞介素-6和干扰素-α可诱导急性巨核细胞白血病（M7）患者原始细胞向巨核细胞分化。造血细胞因子：SCF、IL-3和GM-CSF在体外可保护AML细胞免受化疗诱导的凋亡。最近有许多临床研究报道了评估造血细胞因子：GM-CSF、G-CSF、IL-3和PIXY321作为AML患者化疗辅助药物的效果。大多数研究表明，这些造血细胞因子耐受性良好，在化疗后给予时可有效促进老年AML患者中性粒细胞恢复。另一方面，相当数量的研究在化疗前和化疗期间使用这些细胞因子以使AML细胞进入细胞周期从而使其对化疗更敏感，但未发现有益效果。几项临床试验表明，在难治性和/或复发性AML患者中使用白细胞介素-2作为缓解诱导治疗或作为缓解后巩固性免疫治疗后取得了有前景的结果。化疗后给予造血细胞因子可缩短中性粒细胞减少期和住院时间，而对治疗结果无显著影响。另一方面，在化疗前和化疗期间使用这些细胞因子未带来益处，反而导致一些老年AML患者血小板恢复延迟和生存率更差。
