骨髓增生异常肿瘤进展为伴嗜酸性粒细胞增多的继发性急性髓细胞白血病1例克隆演变分析并文献复习

Clonal evolution of a case with myelodysplastic neoplasms progressed to eosinophilic secondary acute myeloid leukemia and literature review

目的探讨骨髓增生异常肿瘤(MDS)进展为伴嗜酸性粒细胞增多继发性急性髓细胞白血病(s-AML-Eo)患者的克隆演变,并进行相关文献复习。方法选择2017年9月24日于南京医科大学附属常州第二人民医院就诊的1例MDS进展为s-AML-Eo的70岁男性患者为研究对象。采用回顾性分析方法,对本例患者的病史、实验室检查结果、诊疗过程进行分析,对骨髓活组织病理学及细胞形态学检查结果、染色体核型分析和免疫分型、基因检测结果等进行克隆演变分析。本研究以"骨髓增生异常肿瘤""嗜酸性粒细胞""急性髓细胞白血病""克隆演变""myelodysplastic tumor""eosinophils""acute myeloid leukemia""clonal evolution"为中、英文关键词,在中国知网数据库、万方数据知识服务平台、PubMed数据库中,检索s-AML-Eo克隆演变相关文献,并进行文献复习。检索时间设定为以上数据库建库至2022年1月31日。本研究遵循的程序符合2013年修订的《世界医学会赫尔辛基宣言》的要求,并且取得患者知情同意。结果①本例患者因"反复乏力2周"入院,初诊时嗜酸性粒细胞百分比为0.5%。②骨髓细胞形态学检查结果示,由MDS期的骨髓有核细胞增生活跃、原粒细胞比例为7.5%,进展为s-AML-Eo期的骨髓有核细胞增生极度活跃,原粒细胞比例为30%,嗜酸性粒细胞比例为32.5%。③MDS期PDGFRA/B、FGFR1、CBFβ、MLL基因重排均为阴性,进展为s-AML-Eo期后,在计数200个细胞中检出,42个PDGFRB基因重排信号,100个CBFβ基因缺失信号。常见融合基因检测结果均为阴性。TP53p.I255S突变负荷由MDS期的16.1%,提高到s-AML-Eo期的47.5%。④根据本研究设定的文献检索策略,仅检索到1篇相关文献,报道1例18岁AML-M2型女性患者化疗后1年复发,出现嗜酸性粒细胞增多及PDGFRB基因重排的克隆演变。结论MDS患者可进展为s-AML-Eo,并出现嗜酸性粒细胞增多,以及PDGFRB基因重排、CBFβ基因缺失的克隆演变。

Objective To explore the clonal evolution of patients with myelodysplastic neoplasms(MDS)progressed to secondary acute myeloid leukemia with eosinophilia(s-AML-Eo),and review relevant literature.Methods On 24 September 2017,one 70-year-old male patient with MDS progressed to s-AML-Eo who was admitted to affiliated Changzhou Second Hospital of Nanjing Medical University was selected as the research subject.A retrospective analysis method was used to analyze the patient's medical history,laboratory examinations results,diagnosis,and treatment process.The clonal evolution analysis was performed on bone marrow biopsy pathology and cell morphology examination,chromosome karyotype analysis,immune typing,and genetic testing results.Related literature similar to clonal evolution of s-AML-Eo were retrieved from Wanfang Data Knowledge Service Platform,China Medical Journal Network,China National Knowledge Infrastructure and PubMed database,with the key words of"myelodysplastic neoplasms""eosinophils""acute myeloid leukemia""clonal evolution"in Chinese and English.The retrieval time was from the inception of above database to January 31,2022.This study was in line with World Medical Association Declaration of Helsinki revised in 2013 and informed contents were obtained from the subject.Results①The patient was admitted to the hospital due to"recurrent fatigue for 2 weeks",and the eosinophil percentage at the time of initial diagnosis was 0.5%.②The bone marrow cell morphology results showed that the bone marrow nucleated cells in the MDS stage were actively proliferating,and the proportion of myelocytes was 7.5%,then progress to the s-AML-Eo stage,when the bone marrow nucleated cells were extremely active,and the proportion of myelocytes was up to 30%,the proportion of eosinophils was 32.5%.③PDGFRA/B,FGFR1,CBFβand MLL gene rearrangements were all negative in the MDS stage.After progressing to the s-AML-Eo stage,42 PDGFRB gene rearrangement signals and 100 CBFβdeletion signals were counted in 200 cells.Common fusion gene test results are negative.The TP53p.I255S mutation load increased from 16.1%in the MDS stage to 47.5%in the s-AML-Eo stage.④According to the literature retrieval strategy set by this study,only one related document was retrieved,and one case of a 18-year-old AML-M2 female patient was reported,who relapsed at 1 year after chemotherapy.She had eosinophilia and clonal evolution of PDGFRB gene rearrangement.Conclusions MDS patients can progress to s-AML-Eo,with eosinophilia,and clonal evolution of PDGFRB gene rearrangement and CBFβgene deletion.