中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2012年
10期
829-834
,共6页
丁子轩%沈宏杰%缪竞诚%陈苏宁%邱桥成%祁小飞%金正明%吴德沛%何军
丁子軒%瀋宏傑%繆競誠%陳囌寧%邱橋成%祁小飛%金正明%吳德沛%何軍
정자헌%침굉걸%무경성%진소저%구교성%기소비%금정명%오덕패%하군
白血病,非淋巴细胞,急性%DNA突变分析%预后%基因,C-kit%基因,NPM%基因,FLT3
白血病,非淋巴細胞,急性%DNA突變分析%預後%基因,C-kit%基因,NPM%基因,FLT3
백혈병,비림파세포,급성%DNA돌변분석%예후%기인,C-kit%기인,NPM%기인,FLT3
Leukemia%non-lymphoblastic%acute%DNA mutation analysis%Prognosis%Gene,C-kit%Gene%NPM1%Gene%FLT3
目的 探讨急性髓系白血病(AML)患者中C-kit、NPM1、FLT3基因突变的发生率和分布情况,并分析其对预后的影响.方法 应用基因测序方法分别检测656例AML患者C-kit基因8、17号外显子,NPM1基因12号外显子,FLT3基因20(酪氨酸激酶区,TKD)、14、15号外显子(内部串联重复,ITD)基因突变情况,并随访患者的预后.结果 656例AML患者中检出C-kit基因8号外显子突变6例(0.9％),17号外显子突变33例(5.0％),NPM1基因突变169例(25.8％),FLT3-TKD突变46例(7.1％),FLT3-ITD突变178例(27.1％).至少有1个突变的患者341例(50.3％).C-kit的8号外显子检测到6种突变类型；C-kit的17号外显子检测到8种突变类型；NPM1检测到15种突变类型,其中10种类型已有报道(A、B、C、D、Nm、I*、J、J+、S、13),5种类型未见报道；TKD检测到11种突变类型.t(8;21)/M2患者常伴有C-kit的17号外显子突变；inv(16)/M4患者常伴有C-kit的8号外显子突变；M3患者中除FLT3基因突变外未检测到其他突变.NPM1和ITD基因突变多见于正常核型患者,在形态学亚型中多见于M5和M1,阳性病例多伴随高白细胞计数、骨髓原始细胞增多、CD34低表达和CD33高表达.随着发病年龄的增长,突变数量增多,白细胞计数平均值增高,高白细胞计数的患者比例升高.在正常核型的群体中突变阳性的比例较其他群体增高,2种、3种突变的比例增多,差异均有统计学意义(P值均＜0.01).FLT3-ITD突变阳性病例中位生存时间(10.0±1.2)个月,与阴性群体中位生存时间(17.0±2.4)个月相比差异有统计学意义(P =0.004),单独NPM1突变与否对总生存率没有显著影响,但NPM1+/ITD-患者的总生存率最高.结论 C-kit、NPM1、FLT3基因突变类型及数量在MICM分型中都有特殊的分布,并与白细胞计数、骨髓原始细胞数和预后均有相关性.对染色体核型正常的患者,基因突变可作为判断预后新的分子标志.
目的 探討急性髓繫白血病(AML)患者中C-kit、NPM1、FLT3基因突變的髮生率和分佈情況,併分析其對預後的影響.方法 應用基因測序方法分彆檢測656例AML患者C-kit基因8、17號外顯子,NPM1基因12號外顯子,FLT3基因20(酪氨痠激酶區,TKD)、14、15號外顯子(內部串聯重複,ITD)基因突變情況,併隨訪患者的預後.結果 656例AML患者中檢齣C-kit基因8號外顯子突變6例(0.9％),17號外顯子突變33例(5.0％),NPM1基因突變169例(25.8％),FLT3-TKD突變46例(7.1％),FLT3-ITD突變178例(27.1％).至少有1箇突變的患者341例(50.3％).C-kit的8號外顯子檢測到6種突變類型；C-kit的17號外顯子檢測到8種突變類型；NPM1檢測到15種突變類型,其中10種類型已有報道(A、B、C、D、Nm、I*、J、J+、S、13),5種類型未見報道；TKD檢測到11種突變類型.t(8;21)/M2患者常伴有C-kit的17號外顯子突變；inv(16)/M4患者常伴有C-kit的8號外顯子突變；M3患者中除FLT3基因突變外未檢測到其他突變.NPM1和ITD基因突變多見于正常覈型患者,在形態學亞型中多見于M5和M1,暘性病例多伴隨高白細胞計數、骨髓原始細胞增多、CD34低錶達和CD33高錶達.隨著髮病年齡的增長,突變數量增多,白細胞計數平均值增高,高白細胞計數的患者比例升高.在正常覈型的群體中突變暘性的比例較其他群體增高,2種、3種突變的比例增多,差異均有統計學意義(P值均＜0.01).FLT3-ITD突變暘性病例中位生存時間(10.0±1.2)箇月,與陰性群體中位生存時間(17.0±2.4)箇月相比差異有統計學意義(P =0.004),單獨NPM1突變與否對總生存率沒有顯著影響,但NPM1+/ITD-患者的總生存率最高.結論 C-kit、NPM1、FLT3基因突變類型及數量在MICM分型中都有特殊的分佈,併與白細胞計數、骨髓原始細胞數和預後均有相關性.對染色體覈型正常的患者,基因突變可作為判斷預後新的分子標誌.
목적 탐토급성수계백혈병(AML)환자중C-kit、NPM1、FLT3기인돌변적발생솔화분포정황,병분석기대예후적영향.방법 응용기인측서방법분별검측656례AML환자C-kit기인8、17호외현자,NPM1기인12호외현자,FLT3기인20(락안산격매구,TKD)、14、15호외현자(내부천련중복,ITD)기인돌변정황,병수방환자적예후.결과 656례AML환자중검출C-kit기인8호외현자돌변6례(0.9％),17호외현자돌변33례(5.0％),NPM1기인돌변169례(25.8％),FLT3-TKD돌변46례(7.1％),FLT3-ITD돌변178례(27.1％).지소유1개돌변적환자341례(50.3％).C-kit적8호외현자검측도6충돌변류형；C-kit적17호외현자검측도8충돌변류형；NPM1검측도15충돌변류형,기중10충류형이유보도(A、B、C、D、Nm、I*、J、J+、S、13),5충류형미견보도；TKD검측도11충돌변류형.t(8;21)/M2환자상반유C-kit적17호외현자돌변；inv(16)/M4환자상반유C-kit적8호외현자돌변；M3환자중제FLT3기인돌변외미검측도기타돌변.NPM1화ITD기인돌변다견우정상핵형환자,재형태학아형중다견우M5화M1,양성병례다반수고백세포계수、골수원시세포증다、CD34저표체화CD33고표체.수착발병년령적증장,돌변수량증다,백세포계수평균치증고,고백세포계수적환자비례승고.재정상핵형적군체중돌변양성적비례교기타군체증고,2충、3충돌변적비례증다,차이균유통계학의의(P치균＜0.01).FLT3-ITD돌변양성병례중위생존시간(10.0±1.2)개월,여음성군체중위생존시간(17.0±2.4)개월상비차이유통계학의의(P =0.004),단독NPM1돌변여부대총생존솔몰유현저영향,단NPM1+/ITD-환자적총생존솔최고.결론 C-kit、NPM1、FLT3기인돌변류형급수량재MICM분형중도유특수적분포,병여백세포계수、골수원시세포수화예후균유상관성.대염색체핵형정상적환자,기인돌변가작위판단예후신적분자표지.
Objective To evaluate the prevalence and distribution of C-kit,NPM1 and FLT3 gene mutations in patients with acute myeloid leukemia (AML),and to analyze the relationship between the gene mutations and their prognosis.Methods Mutations in exon 8 and 17 of C-kit gene,exon 12 of NPM1 gene,exon 20 of FLT3-TKD gene,and exon 14/15 of FLT3-ITD gene were detected by direct sequencing.Clinical data was collected and followed up if the patient had accepted treatment in our hospital.Results Among the 656 AML patients,mutations in C-kit exon 8 were found in 6 patients (0.9％),C-kit exon 17 in 33(5.0％),NPM1 in 169 (25.8％),FLT3-TKD in46 (7.1％),and FLT3-ITD in 178 (27.1％).Six subtypes of mutations were detected in C-kit exon 8,8 in C-kit exon 17,11 in FLT3-TKD,15 in NPM1,of which 5 were not reported before.C-kit exon 17 mutations were more frequently detected in patients with t(8;21) and exon 8 in patients with inv(16) cytogenetic abnormality.No other gene mutations except FLT3 were detected in M3 patients.NPM1 and ITD mutations were often detected in individuals with normal cytogenetics or M5 and M1 of FAB classification,and accompanied with high white blood cell counts in peripheral blood,high blast counts in bone marrow and low CD34 expression.The older the patients were when diagnosed,the more gene mutations and the higher white blood cell count were detected.More mutations were found in individuals with normal karyotype than that with other karyotypes.It appeared that FLT3-ITD was significantly associated with shorter overall survival (OS) (P =0.004),NPM1 was not significantly associated with OS,but NPM1 +/ITD-patients had the longest OS.Conclusions Our results showed that the mutation types and amounts had particular distribution in MICM subtypes,and were associated with white blood cell counts in peripheral blood,blast counts in bone marrow and prognosis.Especially for patients with normal karyotype,the genetic mutations could be new molecule marker.
