8p11骨髓增殖综合征的临床病理学特征

Clinical Pathological Features of the 8p11 Myeloproliferative Syndrome

本研究旨在提高对罕见的8p11骨髓增殖综合征(eight p11myeloproliferative syndrome,EMS)的临床病理特征、诊断与治疗的认识。应用骨髓细胞涂片、骨髓活检观察细胞形态学改变,流式细胞术检测骨髓细胞的免疫表型,细胞遗传学方法分析骨髓细胞核型,分子生物学检测bcr/abl融合基因。结果表明:EMS是一组具有独特临床和生物学特点的疾病,以bcr/abl阴性的骨髓增殖性肿瘤合并淋巴母细胞淋巴瘤(lymphoblastic lymphoma,LBL)为主要特征。骨髓细胞形态学提示粒系细胞高度增生、嗜酸粒细胞增多;免疫表型分析显示髓系抗原表达增高;细胞遗传学分析表明存在8p11易位;RT-PCR检测bcr/abl融合基因呈阴性。在分子学水平,患者染色体异常均累及8p11上的成纤维细胞生长因子受体-1(FGFR1),目前共发现11种与FGFR1重排相关的伙伴基因,其中最常见的是位于13q11-12上的ZNF-198。EMS预后不良,患者常在短期内进展为急性髓系白血病,常规化疗效果差,除异基因造血干细胞移植外无有效的治疗方法。结论:EMS是伴有FGFR1重排的骨髓和淋巴肿瘤,易误诊为T-LBL、不典型慢性粒细胞白血病(aCML)及慢性粒-单核细胞白血病(CMML),对该病应及时进行细胞遗传学及分子生物学检测,以避免误诊、误治。

This study was aimed to investigate the clinico-pathological features,diagnosis and treatment of the 8p11（eight p11） myeloproliferative syndrome（EMS）.Morphological changes of cells were evaluated by bone marrow smear and biopsy.The cell immunophenotypes were analysed by flow cytometry.Karyotypes were determined by conventional cytogenetic method,and bcr/abl fusion gene was detected by reverse transcription-polymerase chain reaction（RT-PCR）.The results indicated that EMS was a relatively rare disease characterized by the occurrence of a bcr/abl-negative myeloproliferative disorder and a T-cell lymphoblastic lymphoma（T-LBL）.Bone marrow examination showed myeloid hyperplasia or myeloproliferative neoplasm,often accompanied by eosinophilia.Flow cytometric immunophenotyping showed increased myelomonoblasts;cytogenetic analysis showed a translocation at the 8p11 locus;RT-PCR demonstrated non bcr/abl fusion gene.At the molecular level,all cases carryied a chromosomal abnormality involving the fibroblast growth factor receptor 1（FGFR1） at chromosome 8p11.Up to now,11 partner genes have been identified and associated with FGFR1 rearrangements.The most common partner is ZNF198 on chromosome 13q11-12.Majority of patients terminate in acute myeloid leukemia which is resistant to conventional chemotherapy.Currently,the only curative option appears to be allogeneic hematopoietic stem cell transplantation.In conclusion,EMS is myeloid and lymphoid neoplasm,associates with FGFR1 rearrangements.It is usually misdiagnosed as T-LBL,atypical chronic myeloid leukemia（aCML） or chronic myelogenous-monocytic leukemia（CMML）.Timely cytogenetic and molecular biological examination is vital in order to avoid misdiagnosis and mistreatment.