ABL激酶区突变在中国汉族人群伊马替尼耐药Ph+急性淋巴细胞白血病与慢性髓性白血病患者中的分布及特点比较
ABL격매구돌변재중국한족인군이마체니내약Ph+급성림파세포백혈병여만성수성백혈병환자중적분포급특점비교
The different characteristics of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia
  • 万方数据
    中华血液学杂志 중화혈액학잡지
    Chinese Journal of Hematology
    2013年 1期 21-25 ,共5页

    沈宏杰%何军%邱桥成%岑建农%潘金兰%姚利%丁子轩%陈艳%陈子兴

    침굉걸%하군%구교성%잠건농%반금란%요리%정자헌%진염%진자흥

    白血病,淋巴细胞,急性%白血病,髓样,慢性%费城染色体%ABL激酶区%DNA突变分析 白血病,淋巴細胞,急性%白血病,髓樣,慢性%費城染色體%ABL激酶區%DNA突變分析
    백혈병,림파세포,급성%백혈병,수양,만성%비성염색체%ABL격매구%DNA돌변분석
    Leukemia,lymphocytic,actue%Leukemia,myeloid,chronic%Philadelphia chromosome%ABL kinase domain%DNA mutational analysis
    目的 分析ABL激酶区突变在中国汉族人群伊马替尼耐药Ph染色体阳性(Ph+)急性淋巴细胞白血病(ALL)患者中的分布及特点并与慢性髓性白血病(CML)中ABL激酶区突变进行比较.方法 研究对象为2010年10月至2012年4月伊马替尼耐药的122例CML患者及21例Ph+ALL患者.收集CML患者骨髓或外周血单个核细胞及Ph+ALL患者骨髓白细胞,采用TRIzol法抽提总RNA,检测ABL激酶区突变,并结合骨髓细胞形态学、染色体和融合基因结果分析ABL激酶区突变的分布特点.结果 在112例伊马替尼耐药CML患者中检出20个位点23种ABL激酶区突变,突变比例为54.46%(61例),其中P-loop区突变占耐药CML患者的23.21%(26例).在21例伊马替尼耐药Ph+ALL患者中检出8个位点10种突变,突变比例为71.43%(15例),其中T315I突变比例最高,占耐药Ph+ ALL患者的28.57%(6例),其次为E255K/V 19.05%(4例)和Y253F/H 14.29%(3例).T315I突变在耐药Ph+ALL患者中的比例显著高于在耐药CML患者中的比例(P=0.001);Ph+ALL患者使用伊马替尼后出现ABL激酶区突变时间显著短于CML患者(P<0.01);具有额外染色体结构和(或)数目异常的伊马替尼耐药Ph+ALL患者中ABL激酶区突变比例明显高于同组CML患者(P=0.010).结论 ABL激酶区突变在伊马替尼耐药Ph+ALL与CML患者中的主要类型及分布明显不同.具有额外染色体结构和(或)数目异常的耐药Ph+ALL患者中ABL激酶区突变比例显著高于同组CML患者.
    목적 분석ABL격매구돌변재중국한족인군이마체니내약Ph염색체양성(Ph+)급성림파세포백혈병(ALL)환자중적분포급특점병여만성수성백혈병(CML)중ABL격매구돌변진행비교.방법 연구대상위2010년10월지2012년4월이마체니내약적122례CML환자급21례Ph+ALL환자.수집CML환자골수혹외주혈단개핵세포급Ph+ALL환자골수백세포,채용TRIzol법추제총RNA,검측ABL격매구돌변,병결합골수세포형태학、염색체화융합기인결과분석ABL격매구돌변적분포특점.결과 재112례이마체니내약CML환자중검출20개위점23충ABL격매구돌변,돌변비례위54.46%(61례),기중P-loop구돌변점내약CML환자적23.21%(26례).재21례이마체니내약Ph+ALL환자중검출8개위점10충돌변,돌변비례위71.43%(15례),기중T315I돌변비례최고,점내약Ph+ ALL환자적28.57%(6례),기차위E255K/V 19.05%(4례)화Y253F/H 14.29%(3례).T315I돌변재내약Ph+ALL환자중적비례현저고우재내약CML환자중적비례(P=0.001);Ph+ALL환자사용이마체니후출현ABL격매구돌변시간현저단우CML환자(P<0.01);구유액외염색체결구화(혹)수목이상적이마체니내약Ph+ALL환자중ABL격매구돌변비례명현고우동조CML환자(P=0.010).결론 ABL격매구돌변재이마체니내약Ph+ALL여CML환자중적주요류형급분포명현불동.구유액외염색체결구화(혹)수목이상적내약Ph+ALL환자중ABL격매구돌변비례현저고우동조CML환자.
    Objective To identify the distribution and differentiation of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Methods Bone marrow or peripheral blood samples of 112 imatinib resistant CML patients and 21 Ph+ALL patients were obtained from the first affiliated hospital of Soochow university according to local law. Total RNA was extracted from the mononuclear cells using a TRIzol reagent. ABL kinase domain (KD) mutation was detected by direct sequencing. Results Of the 112 imatinib resistant CML patients, 54.46%(61 cases) had ABL KD mutation. Twenty-three mutants were identified in 20 amino acid sites and 23.21% (26 cases) ABL KD mutations were in P-loop region. ABL KD mutations were also detected in 71.43% (15 cases) imatinib resistant Ph+ALL patients, with 10 mutations in 8 amino acid sites. The most frequent mutation was T315I (28.57%), followed by E255K/V (19.05%) and Y253F/H (14.29%). The frequency of T315I was much higher in imatinib resistant Ph+ ALL than that in imatinib resistant CML (P=0.001). Ph+ALL with additional chromosomal aberrations also had a higher rate of ABL KD mutation than that of CML (P=0.010). Ph+ALL gained ABL KD mutation faster than CML(P<0.010). Conclusion Chinese imatinib resistant CML and Ph+ALL patients had different characteristics in ABL KD mutation. The rate of ABL KD mutation in Ph+ALL with additional chromosomal aberrations was much higher than that of CML with additional chromosomal aberrations.
    원문보기 원문다운로드 사이트로이동
저자의 최근 논문