中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2014年
8期
703-707
,共5页
高冠论%许娜%阴常欣%周璇%肖雅娟%李玲%廖立斌%曹睿%徐丹
高冠論%許娜%陰常訢%週璇%肖雅娟%李玲%廖立斌%曹睿%徐丹
고관론%허나%음상흔%주선%초아연%리령%료립빈%조예%서단
白血病,髓系,慢性,BCR-ABL阳性%DNA突变分析%治疗结果%伊马替尼
白血病,髓繫,慢性,BCR-ABL暘性%DNA突變分析%治療結果%伊馬替尼
백혈병,수계,만성,BCR-ABL양성%DNA돌변분석%치료결과%이마체니
Leukemia,myelogenous,chronic,BCR-ABL positive%DNA mutational analysis%Treatment outcome%Imatinib
目的 研究慢性髓性白血病(CML)患者ABL酪氨酸激酶区点突变类型与伊马替尼耐药及预后的关系.方法 收集70例伊马替尼耐药患者骨髓或外周血标本,采用巢式PCR扩增ABL激酶区,纯化后进行双向测序并与同源序列对比,结合患者临床资料进行统计学分析.结果 70例患者中32例(45.7％)检测出ABL酪氨酸激酶区点突变,慢性期、加速期及急变期突变患者分别为16、6、10例,共检测出11种突变类型,分别为T315I、E255K、C475Y、Y253H、G321W、G250E、F317L、E258K、F359V、E459K、F311I.Sokal评分中高危和Ph+染色体伴复杂核型改变是点突变重要的危险因素,点突变与无点突变患者5年累计生存率差异无统计学意义(78.1％对84.2％,P=0.985),但两组无事件生存率差异有统计学意义(34.4％对68.4％,P=0.034).对于点突变患者,异基因造血干细胞移植较二代酪氨酸激酶抑制剂药物或联合化疗有更高的完全细胞遗传学反应率(P=0.001).结论 CML ABL激酶区点突变患者较无突变患者有较差的疗效及预后,及时检测CML慢性期患者ABL激酶区点突变有助于患者治疗方案调整及改善预后,对于疾病进展期点突变患者,异基因造血干细胞移植有相对较好的疗效.
目的 研究慢性髓性白血病(CML)患者ABL酪氨痠激酶區點突變類型與伊馬替尼耐藥及預後的關繫.方法 收集70例伊馬替尼耐藥患者骨髓或外週血標本,採用巢式PCR擴增ABL激酶區,純化後進行雙嚮測序併與同源序列對比,結閤患者臨床資料進行統計學分析.結果 70例患者中32例(45.7％)檢測齣ABL酪氨痠激酶區點突變,慢性期、加速期及急變期突變患者分彆為16、6、10例,共檢測齣11種突變類型,分彆為T315I、E255K、C475Y、Y253H、G321W、G250E、F317L、E258K、F359V、E459K、F311I.Sokal評分中高危和Ph+染色體伴複雜覈型改變是點突變重要的危險因素,點突變與無點突變患者5年纍計生存率差異無統計學意義(78.1％對84.2％,P=0.985),但兩組無事件生存率差異有統計學意義(34.4％對68.4％,P=0.034).對于點突變患者,異基因造血榦細胞移植較二代酪氨痠激酶抑製劑藥物或聯閤化療有更高的完全細胞遺傳學反應率(P=0.001).結論 CML ABL激酶區點突變患者較無突變患者有較差的療效及預後,及時檢測CML慢性期患者ABL激酶區點突變有助于患者治療方案調整及改善預後,對于疾病進展期點突變患者,異基因造血榦細胞移植有相對較好的療效.
목적 연구만성수성백혈병(CML)환자ABL락안산격매구점돌변류형여이마체니내약급예후적관계.방법 수집70례이마체니내약환자골수혹외주혈표본,채용소식PCR확증ABL격매구,순화후진행쌍향측서병여동원서렬대비,결합환자림상자료진행통계학분석.결과 70례환자중32례(45.7％)검측출ABL락안산격매구점돌변,만성기、가속기급급변기돌변환자분별위16、6、10례,공검측출11충돌변류형,분별위T315I、E255K、C475Y、Y253H、G321W、G250E、F317L、E258K、F359V、E459K、F311I.Sokal평분중고위화Ph+염색체반복잡핵형개변시점돌변중요적위험인소,점돌변여무점돌변환자5년루계생존솔차이무통계학의의(78.1％대84.2％,P=0.985),단량조무사건생존솔차이유통계학의의(34.4％대68.4％,P=0.034).대우점돌변환자,이기인조혈간세포이식교이대락안산격매억제제약물혹연합화료유경고적완전세포유전학반응솔(P=0.001).결론 CML ABL격매구점돌변환자교무돌변환자유교차적료효급예후,급시검측CML만성기환자ABL격매구점돌변유조우환자치료방안조정급개선예후,대우질병진전기점돌변환자,이기인조혈간세포이식유상대교호적료효.
Objective To analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia (CML).Methods Nested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain.Then,the amplified product was purified and sequenced in both direction.The homologous analysis was performed in combination of clinical data.Results The ABL domain point mutations were detected in 32 patients (45.7％) including 16 patients in chronic phase (CP),6 patients in accelerated phase (AP) and 10 patients in blast phase (BP),which were detected as T315I,E255K,C475Y,Y253H,G321W,G250E,F317L,E258K,F359V,E459K and F311 I,respectively.Sokal score with intermediate and high risk and Ph+ chromosome with complex karyotype were important risk factors for ABL domain point mutations.The 5-year overall survival (OS) was not significantly different between the patients with or without ABL domain point mutations (78.1％ vs 84.2％,P=0.985),while the 5-year cumulative event-free survival (EFS) of two groups were 34.4％ and 68.4％ (P=0.034),respectively.The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation (allo-HSCT) compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics (P=0.001).Conclusion Patients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations.Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis.And allo-HSCT was a more effective therapy for patients with advanced phase.
