Tam Constantine S, Otero-Palacios Joselle, Abruzzo Lynne V, Jorgensen Jeffrey L, Ferrajoli Alessandra, Wierda William G, Lerner Susan, O'Brien Susan, Keating Michael J
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Br J Haematol. 2008 Apr;141(1):36-40. doi: 10.1111/j.1365-2141.2008.07012.x.
CD20 is an important therapeutic target in chronic lymphocytic leukaemia (CLL). In order to examine the relationship between CD20 expression and cytogenetic abnormalities, we correlated the fluorescent in-situ hybridization (FISH) genetic subtype of 510 treatment-naïve patients with CD20 expression as measured by quantitative flow cytometry. Patients were classified using the Dohner hierarchial classification. The median numbers of CD20 antigen sites by FISH subtypes were: 17p- (n = 26), 9341 per cell; 11q- (n = 42), 5886 per cell; +12 (n = 93), 23 603 per cell; negative FISH (n = 153), 8828 per cell; and 13q- (n = 196), 10 781 per cell. Compared to cases with negative FISH, 11q- cases had significantly lower CD20 expression (P = 0.001), and +12 cases had significantly higher CD20 expression (P < 0.001). The significance of trisomy 12 and high CD20 expression was maintained after multivariate analysis accounting for other disease characteristics. Fifty-nine patients received the combination of rituximab and granulocyte-macrophage colony-stimulating factor as frontline therapy; responses were observed in 13 of 14 (93%) patients with +12, in two of four (50%) patients with 11q-, and in 30 of 41 (73%) patients with negative FISH, 13q- or 17p- CLL. Leukemic CD20 expression differed significantly between FISH subtypes. Patients with trisomy 12 CLL showed strong leukemic cell CD20 expression and had a high rate of response to rituximab-based therapy.
CD20是慢性淋巴细胞白血病(CLL)的一个重要治疗靶点。为了研究CD20表达与细胞遗传学异常之间的关系,我们将510例未经治疗患者的荧光原位杂交(FISH)基因亚型与通过定量流式细胞术测定的CD20表达进行了关联分析。患者采用多纳分级分类法进行分类。FISH各亚型的CD20抗原位点中位数为:17p-(n = 26),每细胞9341个;11q-(n = 42),每细胞5886个;+12(n = 93),每细胞23603个;FISH阴性(n = 153),每细胞8828个;13q-(n = 196),每细胞10781个。与FISH阴性的病例相比,11q-病例的CD20表达显著降低(P = 0.001),而+12病例的CD20表达显著升高(P < 0.001)。在对其他疾病特征进行多因素分析后,12号染色体三体和高CD20表达的意义依然存在。59例患者接受了利妥昔单抗和粒细胞巨噬细胞集落刺激因子联合作为一线治疗;在12号染色体三体的14例患者中有13例(93%)出现反应,11q-的4例患者中有2例(50%)出现反应,FISH阴性、13q-或17p-的CLL患者41例中有30例(73%)出现反应。FISH各亚型之间白血病细胞的CD20表达存在显著差异。12号染色体三体的CLL患者白血病细胞CD20表达较强,对基于利妥昔单抗的治疗反应率较高。