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淋巴细胞表面标志物在急性髓系白血病中的预后价值

Prognostic value of lymphocyte surface markers in acute myeloid leukemia.

作者信息

Ball E D, Davis R B, Griffin J D, Mayer R J, Davey F R, Arthur D C, Wurster-Hill D, Noll W, Elghetany M T, Allen S L

机构信息

Department of Medicine, Dartmouth-Hitchcock Medical Center, Hanover, NH.

出版信息

Blood. 1991 May 15;77(10):2242-50.

PMID:1709379
Abstract

We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

我们研究了339例新诊断的原发性急性髓系白血病(AML)患者骨髓来源的原始细胞上与髓系和淋巴系白血病相关的细胞表面抗原的表达情况,这些患者均参加了癌症与白血病B组(CALGB)化疗方案。令人惊讶的是,在研究CD2(T细胞标志物,T淋巴细胞的绵羊红细胞结合受体)表达的211例病例中,45例呈阳性(21%)。此外,在研究CD19(B淋巴细胞标志物)的298例患者中,41例呈阳性(14%)。总体而言,在同时研究CD2和CD19的170例患者中,56例(33%)呈阳性。有趣的是,对CD2和CD19阳性病例的法美英(FAB)形态学进行中心审查发现,与CD2和CD19阴性病例相比,FAB M3的出现频率是其两倍,M4E的出现频率是其八倍。在22例淋巴细胞抗原阳性病例中,有细胞可用于免疫球蛋白(Ig)或T细胞抗原受体(TCR)基因重排研究,其中20例为种系,1例有重排的Ig重链基因,1例有重排的TCRβ和Ig重链基因。在4例CD2表面抗原阳性病例中证实存在CD2信使核糖核酸,从而验证了细胞表面数据。淋巴细胞抗原阳性病例具有AML中常见的核型;71%有异常克隆的病例有t(8;21)(q22;q22)、16号染色体倒位(p13q22)、t(15;17)(q22;q12)或t(9;11)(p22;q23)。与淋巴细胞抗原阴性的AML患者相比,有淋巴细胞标志物的患者这些核型异常的发生率显著更高(34%对15%,P<0.02)。当将淋巴细胞抗原阳性病例的治疗结果与CD2、CD19阴性病例的治疗结果进行比较时,我们发现CD2、CD19阳性病例实际上有更高的完全缓解率(75%对59%,P = 0.04),以及显著更长的无进展生存期(P = 0.02;2年时为32.4%±6.0%对18.0%±4.1%)和总生存期(P = 0.02;2年时为43.5%±6.3%对26.0%±4.5%)。CD2抗原阳性病例的生存期也显著更优(P = 0.02;2年时为43.8%±7.9%对29.8%±3.8%)。两组在年龄、诊断时白细胞计数、髓外疾病发生率或FAB分类方面无显著差异(P≤0.05)。(摘要截短至400字)

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