Ferrajoli Alessandra, Keating Michael J, Manshouri Taghi, Giles Francis J, Dey Amanda, Estrov Zeev, Koller Charles A, Kurzrock Razelle, Thomas Deborah A, Faderl Stefan, Lerner Susan, O'Brien Susan, Albitar Maher
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Blood. 2002 Aug 15;100(4):1215-9.
Tumor necrosis factor-alpha (TNF-alpha), a cytokine possessing pleiotropic biological activities, is produced by leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) and acts as an autocrine and paracrine growth factor in this disease. In this study, TNF-alpha levels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNF-alpha plasma concentration in the patients with CLL was significantly higher than in the healthy control population (16.4 versus 8.7 pg/mL; P <.0001). Patients having an elevated TNF-alpha level had more advanced Rai and Binet stage disease, higher serum beta(2)-microglobulin (beta(2)M) levels, a greater percentage of cells expressing CD38, and lower hemoglobin and platelet levels. Patients having chromosomal abnormalities such as 11q deletion, trisomy 12, and chromosome 17 aberrations had a higher mean TNF-alpha level (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL; P <.001). The TNF-alpha level was a predictor of survival when the Cox proportional hazards model was used with TNF-alpha entered as a continuous variable (P =.0001). Also, patients having a TNF-alpha level above the mean value of 14 pg/mL had significantly shorter survival duration (P =.00001). The TNF-alpha level remained predictive of survival in Cox multivariate analysis independent of Rai staging and beta(2)M, hemoglobin, prior therapy, white cell count, and platelet level (P =.005). We conclude that the TNF-alpha level serves as a prognostic factor in patients with CLL and that inhibition of TNF-alpha in these patients could have therapeutic importance.
肿瘤坏死因子-α（TNF-α）是一种具有多效生物活性的细胞因子，由慢性淋巴细胞白血病（CLL）患者的白血病淋巴细胞产生，并在该疾病中作为自分泌和旁分泌生长因子发挥作用。在本研究中，测定了150例CLL患者的TNF-α水平，并将其与疾病特征、预后因素和生存率相关联。CLL患者的平均TNF-α血浆浓度显著高于健康对照人群（16.4对8.7 pg/mL；P<.0001）。TNF-α水平升高的患者Rai和Binet分期疾病更晚期，血清β2-微球蛋白（β2M）水平更高，表达CD38的细胞百分比更高，血红蛋白和血小板水平更低。具有11q缺失、三体12和17号染色体畸变等染色体异常的患者平均TNF-α水平（27.5 pg/mL）高于具有二倍体核型或其他杂项细胞遗传学异常的患者（14.2 pg/mL；P<.001）。当将TNF-α作为连续变量纳入Cox比例风险模型时，TNF-α水平是生存的预测指标（P =.0001）。此外，TNF-α水平高于平均值14 pg/mL的患者生存持续时间显著缩短（P =.00001）。在Cox多变量分析中，TNF-α水平仍然是生存的预测指标，独立于Rai分期、β2M、血红蛋白、既往治疗、白细胞计数和血小板水平（P =.005）。我们得出结论，TNF-α水平可作为CLL患者的预后因素，并且在这些患者中抑制TNF-α可能具有治疗意义。
