Lin Thomas S, Flinn Ian W, Modali Rama, Lehman Teresa A, Webb Jennifer, Waymer Sharon, Moran Mollie E, Lucas Margaret S, Farag Sherif S, Byrd John C
Department of Medicine, Division of Hematology-Oncology, The Ohio State University, Columbus 43210, USA.
Blood. 2005 Jan 1;105(1):289-91. doi: 10.1182/blood-2004-02-0651. Epub 2004 Jun 24.
The in vivo mechanism of action of alemtuzumab (anti-CD52; Campath-1H) remains unclear. With rituximab, FCGR3A and FCGR2A high-affinity polymorphisms have been associated with clinical response in lymphoma but not in CLL, suggesting potential divergent mechanisms of action between these 2 diseases. Herein, we examined FCGR3A (V/V, n = 4; V/F, n = 10; F/F, n = 19) and FCGR2A (A/A, n = 5; H/A, n = 22; H/H, n = 6) polymorphisms in 36 patients with relapsed CLL who were treated with thrice-weekly alemtuzumab for 12 weeks to assess the potential influence these high-affinity FcgammaR receptor polymorphisms had on response to alemtuzumab. Response to alemtuzumab was similar regardless of FCGR3A polymorphism (V/V, 25%; V/F, 40%; F/F, 32%) or FCGR2A polymorphism (A/A, 40%; H/A, 32%; H/H, 33%). These findings indicate that FCGR3A and FCGR2A polymorphisms may not predict response to alemtuzumab in CLL. Future studies examining larger cohorts of alemtuzumab-treated patients with CLL will be required to definitively determine the predictive value of specific FCGR polymorphisms to treatment response.
阿仑单抗（抗CD52；Campath-1H）的体内作用机制仍不清楚。对于利妥昔单抗，FCGR3A和FCGR2A的高亲和力多态性与淋巴瘤的临床反应相关，但与慢性淋巴细胞白血病（CLL）无关，这表明这两种疾病之间可能存在不同的作用机制。在此，我们检测了36例复发CLL患者的FCGR3A（V/V，n = 4；V/F，n = 10；F/F，n = 19）和FCGR2A（A/A，n = 5；H/A，n = 22；H/H，n = 6）多态性，这些患者接受每周三次阿仑单抗治疗12周，以评估这些高亲和力FcγR受体多态性对阿仑单抗反应的潜在影响。无论FCGR3A多态性（V/V，25%；V/F，40%；F/F，32%）或FCGR2A多态性（A/A，40%；H/A，32%；H/H，33%）如何，对阿仑单抗的反应相似。这些发现表明，FCGR3A和FCGR2A多态性可能无法预测CLL患者对阿仑单抗的反应。需要进一步研究检测更大队列接受阿仑单抗治疗的CLL患者，以明确确定特定FCGR多态性对治疗反应的预测价值。
