伴有嗜酸粒细胞增多的血液病临床和实验研究

Clinical and laboratory characteristics of hematological diseases associated with eosinophilia

目的探讨伴有嗜酸粒细胞增多的血液病患者的临床和分子、细胞遗传学特征。方法对44例伴有嗜酸粒细胞增多血液病患者的骨髓标本，经直接法和24h短期培养后按常规方法制备染色体，采用R显带技术进行细胞遗传学分析；分别应用PDGFRα、PDGFRβ、FGFR1基因探针，进行荧光原位杂交（FISH）检测。结果44例患者骨髓细胞经常规染色体核型分析，异常核型检出率为13．64％（44例中6例），而应用FISH技术分析，异常克隆检出率为29．55％（44例中13例），其中7例（15．91％）伴有FIPILI—PDGFRα（简称F／P）融合基因，3例（6．82％）PDGFRα基因重排，2例（4．55％）PDGFRβ基因异常，1例（2．27％）FGFR1基因重排。将患者分为PDGFRα、PDGFRβ或FGFR1基因重排阳性（13例）与阴性（31例）组，阳性组患者的皮肤、心血管、脾脏、肺脏等器官受累程度以及WBC、PLT、HGB等血液学指标与阴性组患者无明显差异；与阴性组比较，阳性组患者胃肠道症状表现较为突出，且绝大多数患者外周血白细胞分类可见嗜酸粒细胞重度增高（绝对值〉5×10^9／L）以及骨髓中出现幼稚嗜酸粒细胞（P值均〈0．05）。结论伴有嗜酸粒细胞增多的血液病患者具有独特的临床和血液学特征。染色体核型分析与FISH方法结合具有较高的异常克隆（特别是PDGFRα基因异常）检出率，有助于鉴别疾病的良、恶性本质，判断预后及选择合理的治疗方案。

Objective To analyze the clinical and laboratory characteristics of hematological diseases associated with eosinophilia. Methods Karyotype analysis was performed by direct method and/or short-time culture of bone marrow cells for R-banding. Fluorescence in situ hybridization （FISH） was performed using PDGFRα, PDGFRβ and FGFR1 break-apart probes. Results The clinical and hematological findings of 44 patients were diagnosed as hematological diseases associated with eosinophilia. Abnormal karyotypes were detected in 6 cases （ 13.64% ） with karyotyping. The efficiency of the detection of abnormal clone was markedly increased to 29.55% （13/44） with FISH techniques, including 7 cases with FIP1L1-PDGFRα （ F/P, 15.91% ）, 3 （6. 82% ） PDGFRα rearrangement, 2 （4. 55% ） aberrant PDGFRβ gene and 1 （2. 27% ） FGFR1 rearrangement. Patients being PDGFRα, PDGFRβ or FGFRI positive （13 cases） or negative （31 cases） showed predominant difference in clinical and laboratory features. The incidence of gut involvement, the absolute count of eosinophils in peripheral blood and the percentage of immature eosinophils in bone marrow were significantly increased in positive patients （P 〈 0.05 ）. Conclusions The hematological diseases associated with eosinophilia are characterized by unique clinical and laboratory features. Karyotyping should be a routine approach to detect the abnormal clone in these diseases. Screening for PDGFRα, PDGFRβ and FGFR1 gene with FISH can provide more genetic information.