急性白血病细胞中CD19的表达及其意义

目的 观察CD19在儿童急性白血病(AL)中的表达与分布,为白血病的诊断、鉴别以及导向治疗提供依据。方法 采用27个荧光直标单克隆抗体(简称单抗)及CD45／SSC双参数设门多色流式细胞术对210例儿童AL细胞进行免疫诊断和分型,并对CD19在各种类型AL细胞中的表达情况进行分析。结果在93例急性淋巴细胞性白血病(ALL)病例中,CD19的阳性率(99％,92／93)明显高于B细胞系其他相关抗原的阳性率,如CD10(88％,82／93,P=0．003)、CD20)(25％,23／93,P=0．001)和CD22(60％,56／93,P=0．001);CD19在9例含B系成分的杂合型白血病(hybrid acuteleukemia,HAL)中全部表达,而在24例T细胞系ALL和5例T／My(髓)HAL上均无表达;在79例急性髓系白血病(AML)中,仅5例(6％)CD19阳性,明显低于它在B系ALL中的阳性率(99%,P=0．001)。结论 CD19对B系ALL细胞的特异性较好,敏感性高,在B细胞系各个分化阶段持续稳定表达,是诊断B系ALL较为可靠的表面标记,也可作为导向治疗B系ALL的理想靶点。

The expression of CD19 in 210 cases of childhood acute leukemia and its significance

OBJECTIVE: To investigate the expression of CD19 on childhood acute leukemia (AL) and its significance, and to provide evidence for the diagnosis and differential diagnosis as well as monoclonal antibody-targeting treatment of leukemia. METHODS: There were 210 cases of childhood AL, of which 130 cases were male and 80 were female with a mean age of 9 years old. Using a panel of 27 fluorochrome directly labeled monoclonal antibodies, 210 samples from the patients were analyzed with CD45/SSC double parameters and multi-color flow cytometry to determine the expression of CD19. RESULTS: In the 93 cases of B lineage acute lymphoblastic leukemia (ALL), the positive rate (98.9%, 92/93) of CD19 was significantly higher than that of the other B cell related antigens, such as CD10 (88.2%, 82/93, P = 0.003), CD20 (24.7%, 23/93, P = 0.001) and CD22 (60.2%, 56/93, P = 0.001). CD19 was expressed on all 8 cases of B/myeloid (My) hybrid acute leukemia (HAL) and 1 case of B/T HAL, but was not expressed on all 24 cases of T lineage leukemia and 5 cases of T/My HAL. In the 79 cases of acute myeloid leukemia (AML), only 5 (6.3%) cases expressed CD19. The positive rate (6.3%) of CD19 on AML was significantly lower than that on B lineage ALL (98.9%, P = 0.001). The percentage of CD19 positive cells in B/My HAL (41.6% - 88.7% with a mean of 73.8%) was significant higher than that in CD19(+)-AML (21.4% - 50.4% with a mean of 24.2%; Run Sum test, P = 0.0084). Of the 210 cases, 102 were B lineage related AL including B lineage ALL, B/My HAL and B/T HAL. In B lineage related AL, the sensitivity and the specificity of CD19 was 99.0% (101/102) and 95.4% (13/108) while the positive predictive and the negative predictive values to B lineage were 95.3% (101/106) and 99.0% (103/104), respectively. Using CD19(+) as a single reagent to diagnose B lineage, the false positive rate was 4.6% (5/108) and the false negative rate was 1.0% (1/102) with a general diagnosis index (GDI) of 94.4% [GDI = 1-(false positive rate + false negative rate)]. CONCLUSION: CD19 is continuously and stably expressed on all stages of B lineage differentiation. It is a reliable cell membrane marker for diagnosing B lineage ALL and an ideal target for antibody-targeting treatment of leukemia as well; the expression degree of CD19 can be used to distinguish B/My HAL from CD19(+)-AML; CD19 didn't express on normal myeloid cells but did on some AML cells. Therefore it can be used to detect the minimal residual disease.