Elias L, Van Epps D E, Smith K J, Savage B
Cancer Center, University of New Mexico School of Medicine, Albuquerque.
Leukemia. 1987 Feb;1(2):111-5.
Because qualitative neutrophil and platelet dysfunction is an important concomitant of the myelodysplastic syndrome, functional studies were performed prospectively of cells from eight patients with myelodysplastic syndrome undergoing treatment with recombinant alpha 2 interferon. Neutrophil studies performed included myeloperoxidase release and superoxide anion generation, measured spectrophotometrically, in response to stimulation by phorbol-12-myristate-13-acetate, opsonized zymosan, and the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP), respectively. The most consistently abnormal of these tests was the fMLP-stimulated superoxide anion generation, which was low in six of seven patients tested. Mean results with this test were significantly lower than controls (mean +/- SD = 5.11 +/- 2.41 nmol/10(6) patient cells vs. 10.14 +/- 3.02 with normal cells, p less than 0.001). No significant change was noted following 2 or 8 weeks of interferon therapy. Because of the severe thrombocytopenia prevalent in myelodysplastic syndrome, fewer platelet studies were feasible. One patient, however, exhibited normal platelet numbers but markedly decreased aggregation in response to arachidonic acid, epinephrine, and collagen. After 4 weeks of treatment, this patient's platelet aggregation was noted to be normal. Platelets from two patients were purified by gel filtration, and the ATP/ADP ratios were determined by HPLC. Pretreatment ATP/ADP ratio of one patient was 4.85 (normal = 1.85 +/- 0.28) which declined to 3.27 on treatment and then returned to 4.80 following a 14-day period off treatment. Another patient, also with elevated ATP/ADP, exhibited a smaller decline during a treatment cycle. From these studies it was concluded that fMLP-stimulated superoxide generation may be a sensitive marker for neutrophil dysfunction in the myelodysplastic syndrome. No evidence was found for improvement of neutrophil dysfunction following alpha 2 interferon treatment. alpha 2 interferon, however, may sometimes have beneficial effects upon platelet dysfunction.
由于定性中性粒细胞和血小板功能障碍是骨髓增生异常综合征的重要伴随症状，因此对8例接受重组α2干扰素治疗的骨髓增生异常综合征患者的细胞进行了前瞻性功能研究。进行的中性粒细胞研究包括髓过氧化物酶释放和超氧阴离子生成，分别通过分光光度法测量，以响应佛波醇-12-肉豆蔻酸酯-13-乙酸酯、调理酵母聚糖和趋化肽甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）的刺激。这些测试中最一致异常的是fMLP刺激的超氧阴离子生成，在7例测试患者中有6例该指标较低。该测试的平均结果显著低于对照组（平均±标准差=5.11±2.41 nmol/10⁶患者细胞，正常细胞为10.14±3.02，p<0.001）。干扰素治疗2周或8周后未观察到显著变化。由于骨髓增生异常综合征中普遍存在严重血小板减少症，可行的血小板研究较少。然而，1例患者血小板数量正常，但对花生四烯酸、肾上腺素和胶原的聚集明显减少。治疗4周后，该患者的血小板聚集恢复正常。通过凝胶过滤纯化了2例患者的血小板，并通过高效液相色谱法测定ATP/ADP比值。1例患者治疗前的ATP/ADP比值为4.85（正常=1.85±0.28），治疗时降至3.27，停药14天后又恢复到4.80。另1例ATP/ADP也升高的患者在一个治疗周期中的下降幅度较小。从这些研究得出结论，fMLP刺激的超氧生成可能是骨髓增生异常综合征中性粒细胞功能障碍的敏感标志物。未发现α2干扰素治疗后中性粒细胞功能障碍有改善的证据。然而，α2干扰素有时可能对血小板功能障碍有有益作用。
