CAJ | 학술논문

目的探讨再生障碍性贫血(AA)单体7(-7)克隆的演变.方法应用间期荧光原位杂交(FISH)技术分析81例核型正常的初诊AA患者及46例免疫抑制联合重组人粒细胞集落刺激因子(rhuG-CSF,疗程大于6个月)治疗后AA患者的-7克隆.结果 81例初诊AA患者中,11例(13.6%)-7克隆阳性,阳性细胞比例5.4%～7.6%,-7克隆阳性患者疗效及生存率与-7克隆阴性者相比差异无统计学意义(P值分别为0.481和0.865),11例阳性患者(包括5例rhuG-CSF疗程大于6个月者)治疗后-7比例均下降至正常,中位随访时间44个月,未发现转化为骨髓增生异常综合征(MDS)或急性髓系白血病(AML)的证据;追踪随访46例AA患者的-7克隆,治疗后3～6个月均为阴性,治疗后12～15个月5例阳性,中位随访时间48个月,FISH共检测到6例-7克隆阳性,均进展为MDS或AML,5例为-7核型.FISH检出阳性克隆的时间较常规核型分析提前3～18个月;应用HSH技术回顾性分析了4例转化为MDS或AML的AA患者初诊时标本,-7克隆均为阴性.结论部分初诊AA患者具有潜在低比例的-7克隆,但与治疗反应及最终进展为克隆性疾病无关;rhuG-CSF可能促进-7克隆扩增,长期应用rhuG-CSF治疗的AA患者需用间期FISH技术密切监测异常克隆.
목적 탐토재생장애성빈혈(AA)단체7(-7)극륭적연변.방법 응용간기형광원위잡교(FISH)기술분석81례핵형정상적초진AA환자급46례면역억제연합중조인립세포집락자격인자(rhuG-CSF,료정대우6개월)치료후AA환자적-7극륭.결과 81례초진AA환자중,11례(13.6%)-7극륭양성,양성세포비례5.4%～7.6%,-7극륭양성환자료효급생존솔여-7극륭음성자상비차이무통계학의의(P치분별위0.481화0.865),11례양성환자(포괄5례rhuG-CSF료정대 우6개월자)치료후-7비례균하강지정상,중위수방시간44개월,미발현전화위골수증생이상종합정(MDS)혹급성수계백혈병(AML)적증거;추종수방46례AA환자적-7극륭,치료후3～6개월균위음성,치료후12～15개월5례양성,중위수방시간48개월,FISH공검측도6례-7극륭양성,균진전위MDS혹AML,5례위-7핵형.FISH검출양성극륭적시간교상규핵형분석제전3～18개월;응용HSH기술회고성분석료4례전화위MDS혹AML적AA환자초진시표본,-7극륭균위음성.결론 부분초진AA환자구유잠재저비례적-7극륭,단여치료반응급최종진전위극륭성질병무관;rhuG-CSF가능촉진-7극륭확증,장기응용rhuG-CSF치료적AA환자수용간기FISH기술밀절감측이상극륭.
Objective To explore the clonal evolution of monosomy 7 in patients with aplastic anemia (AA).Methods Monosomy 7(-7)in 81 AA patients with normal karyotype at diagnosis and 46 AA treated with innnunosuppressive therapy(IST)and more than 6 months of recombinant human granulocyte colonystimulating factor(rhuG-CSF)were detected by interphase-fluorescence in situ hybridization(FISH)retrospectively.Results There were 5.4%-7.6% of-7 cells in 11(13.6%)of 81 patients at diagnosis,the survival and response rate to IST in-7 positive patients did not differ significantly from that in-7 negative patients(P = 0.481,0.865);-7 cells disappeared after IST in all of the 11 patients including 5 received long-term rhuG-CSF therapy,and none of them evolved to myelodysplastic syndromes/acute myeloid leukemia (MDS/AML)at a median follow-up of 44 months.Serial assessments of-7 clones were performed in 46 patients,none of whom detected-7 clones 3-6 months after IST,but-7 recurrence in 5 patients 12-15months after IST.At a median follow-up of 48 months,FISH identified 6 patients with-7 clones while the conventional cytogenetic analysis(CCA)recognized in 5.Moreover,the first demonstration of-7 by FISH was 3-18 months earlier than that by CCA.All of the 6 patients with FISH detected-7 evolved to MDS/AML with-7 and four of them were retrospectively analysed for in samples at-7 diagnosis of AA,but none of them was positive.Conclusions Monosomy 7 exists in a part of AA patients,but the preexisting-7 cells seems neither associated with fatality nor evolvation to MDS/AML.rhuG-CSF might facilitate the expansion of -7 clones;It is necessary to monitor-7 in AA,especially when received long-term rhuG-CSF therapy.