Section of Hematology, Department of Medicine, University of Verona, Piazzale L A Scuro 10, Verona, Italy.
Eur J Haematol. 2011 Sep;87(3):228-34. doi: 10.1111/j.1600-0609.2011.01650.x. Epub 2011 Jul 26.
A proliferation-inducing ligand (APRIL), a tumor necrosis factor superfamily member involved in B-lymphocytes differentiation and survival, plays a role in protecting B-Cell Chronic lymphocytic leukemia (B-CLL) cells from apoptosis. Having observed that APRIL serum (sAPRIL) levels were higher in B-CLL patients with CLL at diagnosis as compared to healthy donors (14.61±32.65 vs. 4.19±3.42 ng/mL; P<0.001), we tested the correlation existing in these patients between sAPRIL, clinical-biological parameters and disease progression.
sAPRIL levels were measured by ELISA in 130 patients with B-CLL at diagnosis and in 25 healthy donors.
sAPRIL levels did not correlate with gender, age, clinical stage, blood cell counts, β2-microglobulin (β2M) levels, ZAP-70 and CD38 expression. Using median sAPRIL natural logarithm (ln) as cutoff, we distinguished two groups of patients (APRIL(LOW) and APRIL(HIGH) ) who were comparable with regard to clinical-biological parameters and overall survival, but different with regard to time to the first treatment (TTFT; P=0.035). According to univariate analysis, high lymphocyte count, high β2M, Binet stage B-C, ZAP-70 expression and ln(sAPRIL) above median were associated with earlier TTFT. Advanced clinical stage, high β2M, ZAP-70 expression and ln(sAPRIL) above median remained independently predictive of shorter TTFT at multivariate analysis. Moreover, sAPRIL increased its prognostic significance when patients were stratified according to independent favorable clinical-biological characteristics (low β2M, stage A and lack of ZAP-70 expression).
sAPRIL is a novel indicator of shorter TTFT in B-CLL and a predictor of progression especially in patients otherwise considered at low risk according to validated prognostic factors.
增殖诱导配体（APRIL）是肿瘤坏死因子超家族成员，参与 B 淋巴细胞分化和存活，在保护 B 细胞慢性淋巴细胞白血病（B-CLL）细胞免于凋亡方面发挥作用。我们观察到，与健康供体相比，初诊时 B-CLL 患者的 APRIL 血清（sAPRIL）水平更高（14.61±32.65 与 4.19±3.42ng/mL；P<0.001），因此我们在这些患者中测试了 sAPRIL 与临床生物学参数和疾病进展之间的相关性。
采用 ELISA 法检测 130 例 B-CLL 患者和 25 例健康供体的 sAPRIL 水平。
sAPRIL 水平与性别、年龄、临床分期、血细胞计数、β2-微球蛋白（β2M）水平、ZAP-70 和 CD38 表达无关。使用 sAPRIL 自然对数（ln）中位数作为截点，我们将患者分为两组（APRIL（LOW）和 APRIL（HIGH）），两组在临床生物学参数和总生存方面无差异，但在首次治疗时间（TTFT）方面存在差异（P=0.035）。根据单因素分析，高淋巴细胞计数、高β2M、Binet 期 B-C、ZAP-70 表达和 ln（sAPRIL）高于中位数与 TTFT 较早相关。多因素分析显示，晚期临床分期、高β2M、ZAP-70 表达和 ln（sAPRIL）高于中位数与 TTFT 较短独立相关。此外，当根据独立的有利临床生物学特征（低β2M、A 期和缺乏 ZAP-70 表达）对患者进行分层时，sAPRIL 增加了其预后意义。
sAPRIL 是 B-CLL 中 TTFT 较短的新指标，特别是在根据验证的预后因素被认为风险较低的患者中，是疾病进展的预测因子。
