一例伴有PDGFRA和EVI1重排的髓系肿瘤患者的临床和遗传学特征

摘要

目的 提高对伴有PDGFRA和EVI1重排的髓系肿瘤患者的临床及遗传学特征的认识.方法 收集1例同时伴有PDGFRA和EVI1基因重排的髓系肿瘤患者的临床资料,应用常规细胞遗传学方法、荧光原位杂交技术和巢式PCR进行遗传学分析.结果 患者临床表现主要为反复皮疹、关节肿痛及间断发热,外周血白细胞计数明显升高、嗜酸细胞增多,体检示巨脾;骨髓病理示骨髓组织明显增生、嗜酸细胞明显增多;染色体核型分析显示患者染色体核型为46,XY,t(3;5) (q26;q15)[6]/46,XY[10];荧光原位杂交结果显示PDGFRA及EVI1基因重排均为阳性,巢式PCR证实FIP1 L1/PDGFRA阳性.患者经单药伊马替尼(200 mg/d)治疗后临床症状缓解.随访期实时定量PCR检测结果显示FIP1L1/PDGFRA转录本水平逐渐下降,并在治疗第10个月转为阴性,但EVI1表达水平与健康对照相比无明显差异且稳定不变.结论 同时伴有PDGFRA和EVI1重排的髓系肿瘤患者具有独特的临床及遗传学特征,分子遗传学检查有助于早期诊断,单药小剂量伊马替尼治疗有效.%Objective Todelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements.Methods Clinical data of the patient was collected.Conventional cytogenetics,fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient.Results The patient has featured recurrent rash,joint pain,and intermittent fever.Laboratory tests showed hyperleukocytosis and marked eosinophilia.Physical examination revealed splenomegaly.His karyotype was 46,XY,t (3;5) (q26;q1 5) [6]/46,XY[10].FISH assay showed that both PDGFRA and EVI1 genes were rearranged.Molecular studies of the mRNA suggested that there was a in-frame fusion between exon 12 of the PDGFRA gene and exon 9 of the FIP1L1 gene.Imatinib was initiated at a dosage of 200 mg,and after 10 months,the signal of the FIP1L1-PDGFRA fusion gene was undetectable in bone marrow sample.However,the expression of EVI1 mRNA was stable,with no significant difference found between the patient and 10 healthy controls.Conclusion MPN in association with PDGFRA and EVI1 genes rearrangements have unique clinical and genetic features.Genetic testing is helpful for early diagnosis.Imatinib may be effective for the treatment.