伴AML-1/ETO融合基因的急性髓细胞白血病M_2型患者骨髓的多参数免疫表型特征

Multiparametric immunophenotypic features of acute myelocytic leukemia-M_2 patients with AML-1/ETO fusion gene

目的探讨伴 AML-1/ETO 基因重排的急性髓细胞白血病 M_2型(AML-M_2)患者骨髓的多参数免疫表型特征及多参数免疫表型检测对此亚型的预测性。方法应用多参数流式细胞术分析30例经荧光原位杂交(FISH)检测 AML-1/ETO 融合基因阳性,FAB 分型为 AML-M_2(简称 M_2/ETO^+)患者骨髓的免疫表型,并与36例 FAB 分型为 AML-M_2、AML-1/ETO 融合基因检测为阴性(简称 M_2/ETO^-)和34例 FAB 分型为 AML-M_3(急性早幼粒细胞白血病,APL)患者的免疫表型进行比较。结果 30例 M_2/ETO^+患者骨髓中均可见一群原始细胞(15.89%～68.53%)和一群侧向散射(SSC)较高异质性、分化的粒细胞。原始细胞表达干细胞相关抗原 CD_(34)、HLA-DR 和髓系抗原 CD_(33)、CD_(13)、MPO,并显示特异的抗原表达模式。在 M_2/ETO^+患者中 CD_(33)表达的平均荧光强度显著低于M_2/ETO^-和 APL 患者(MFI 分别为98±75、244±184和845±523,P 均<0.01),CD_(19)(90.0%)和CD_(34)^+CD_(56)^+(100%)共表达的阳性率均显著高于 M_2/ETO^-(11.11%,25.0%)和 APL 患者(8.82%,0%),P 均<0.01,与 APL 比较 CD_9^+MPO^+的共表达率显著降低(0%vs.93.75%),而 HLA-DR 表达则显著升高(100%vs.27.27%)。M_2/ETO^+患者粒细胞表达分化的髓系抗原 CD_(11b)和 CD_(15),并可分为 CD_(15)^+CD_(11b)^-和 CD_(15)^+CD_(11b)^+两群,而成熟的粒细胞标志 CD_(10)均为阴性,并且81.48%M_2/ETO^+患者的粒细胞表达 CD_(56),显著高于 M_2/ETO^-患者(22.22%)和 APL 患者(17.56%)。结论伴 AML-1/ETO 基因重排的 AML-M_2型白血病具有独特的免疫表型,对其基因重排有较高的预测性。应用多参数免疫分型技术可较容易地将 M_2/ETO^+亚型白血病与 APL 鉴别。

Objective To investigate multiparametric immunophenotypic features in patients with acute myelocytic leukemia （AML）-M2 bearing AML-1/ETO gene rearrangements and its predicting value. Methods A multiparametric flow cytometry was used in the study of phenotypic characterization of the subtype of AML. Immunophenotype of 30 patients with AML （ M2/ETO^＋ ） was analyzed by fluorescence in situ hybridization （FISH）. The results were compared with 36 patients of AML-M2 with AML-1/ETO^- （M2/ETO^-） and 34 acute promyelocytic leukemia （APL） patients. Results There were a population. 15.89%-68.53% the blast cell and a population of more differentiated and heterogeneous myeloid cells in the marrow of 30 patients with M2/ETO^＋. The blast cells had a myeloid phenotype （CD33, CD13 and MPO） and showed a characteristic pattern of antigen expression. The fluorescent intensity of CD33 in patients with M2/ETO^＋ was less than in patients with M2/ETO^- and APL [ mean fluorescent intensity（MFI） ：98 ± 75 v. 244 ± 184 and 845 ± 523 ,both P 〈 0. 01 ]. The patients with M2/ETO^＋ showed higher expression of CD19 （27/30, 90. 0% ） and coexpression of CD34^＋CD56^＋ （27/27, 100% ） compared with M2/ETO^- （4/36, 11.11% ; 9/36, 25.0% ） and APL （3/34, 8.82% ; 0/34, 0% ） ,and a lower positive rate of CD9^＋MPO^＋ （0/14, 0%） and higher positive of HLA-DR （30/30, 100% ） than APL （30/32, 93.75% and 9/33, 27.27% ）. The granulocytic differentiation antigen CD15/CD11b was present in the patients of M2/ETO^＋. It could be divided into CD15^＋CD11b^- and CD15^＋CD11b^＋. The granulocytes significantly expressed CD56 （ 22/27, 81.48% ） in patients with M2/ETO^＋ compared to patients with M2/ETO^-（ 8/36, 22. 22% ） and patients with APL （6/34, 17.56% ）. Conclusion The AML-M2 patients with AML-1/ETO gene rearrangements displays an exclusive immunophenotype which is highly predictive of the gene rearrangement and can be use to differentiate M2/ETO^＋ from APL.