BAP1及TET2蛋白在慢性粒-单核细胞白血病患者骨髓中的表达及其意义

Expressions of BAP1 and TET2 proteins in bone marrow of patients with chronic myelomonocytic leukemia and their significances

目的探讨BAP1与TET2蛋白在慢性粒-单核细胞白血病(CMML)患者骨髓中的表达及其与CMML预后的关系。方法收集2003年9月至2007年5月上海市中美联合白血病协作组确诊的41例成年CMML患者现存的骨髓石蜡标本,采取石蜡切片免疫组织化学法重新检测BAP1和TET2蛋白表达,同时收集同期确诊的40例成年急性粒-单核细胞白血病(AMML)患者和20例缺铁性贫血(IDA)患者现存的骨髓石蜡标本作为对照,采用相同方法检测TET2和BAP1蛋白表达情况。采用回顾性队列研究方法分析41例CMML患者的临床资料,计数资料的比较采用χ^2检验,采用Pearson相关分析法分析BAP1和TET2蛋白表达间的关系,应用Log-rank检验进行单因素分析,应用Kaplan-Meier法进行生存分析。结果41例CMML患者中,BAP1阳性表达率为31.7%(13/41),其中CMML-1型患者为28.6%(8/28),CMML-2型为38.5%(5/13);TET2阳性表达率为41.5%(17/41),其中CMML-1型患者为39.3%(11/28),CMML-2型患者为46.2%(6/13)。40例AMML患者中,BAP1阳性表达率为32.5%(13/40),TET2阳性表达率为35.0%(14/40)。20例IDA患者中,BAP1阳性表达率为5.0%(1/20),TET2无阳性表达。CMML-1型和CMML-2型患者间BAP1和TET2阳性表达率差异均无统计学意义(χ^2=0.40,P=0.53;χ^2=0.17,P=0.68)。CMML与AMML患者间BAP1和TET2阳性表达率差异均无统计学意义(χ^2=0.01,P=0.94;χ^2=0.36,P=0.64)。血液系统肿瘤性疾病(CMML+AMML)和血液系统非肿瘤性疾病(IDA)间BAP1和TET2阳性表达率差异均有统计学意义(χ^2=6.01,P<0.05;χ^2=11.04,P<0.01)。Pearson相关分析显示,BAP1和TET2表达之间无相关性(r=0.35,P=0.27)。单因素分析显示,重度贫血(血红蛋白<60 g/L)、单核细胞计数≥2.0×10^9/L、中性粒细胞计数<1.5×10^9/L、染色体异常核型是CMML不良预后因素。BAP1和TET2表达均与CMML患者的预后无关(χ^2=0.28,P=0.600;χ^2=0.53,P=0.460)。结论BAP1及TET2蛋白在CMML患者中均有较高阳性表达率,但其表达均与患者预后无关。

ObjectiveTo investigate the expressions of BAP1 and TET2 proteins in bone marrow of patients with chronic myelomonocytic leukemia(CMML)and their relationship with the prognosis of CMML.MethodsThe bone marrow paraffin specimens of 41 cases from 41 adult CMML patients diagnosed by Shanghai Sino-US Joint Leukemia Coordination Group from September 2003 to May 2007 were collected.The immunohistochemistry was used to detect the expressions of BAP1 and TET2 proteins in 41 CMML patients.The expressions of TET2 and BAP1 proteins were also detected by the same method in 40 adult patients with acute myelomonocytic leukemia(AMML)and 20 patients with iron deficiency anemia(IDA)diagnosed at the same time as the comparison.The clinical data of 41 CMML patients were analyzed by using retrospective cohort study.The count data were compared by using chi-square test.The correlation between expressions of BAP1 and TET2 proteins was analyzed by using Pearson correlation analysis.Kaplan-Meier method was used to calculate the survival time,and Log-rank test was used for single factor analysis.ResultsIn 41 CMML patients,the positive expression rate of BAP1 was 31.7%(13/41),including 28.6%(8/28)in CMML-1 patients and 38.5%(5/13)in CMML-2 patients;the positive expression rate of TET2 was 41.5%(17/41),including 39.3%(11/28)in CMML-1 patients and 46.2%(6/13)in CMML-2 patients.In 40 AMML patients,the positive expression rate of BAP1 was 32.5%(13/40),and the positive expression rate of TET2 was 35.0%(14/40).In 20 IDA patients,the positive expression rate of BAP1 was 5.0%(1/20),and TET2 had no positive expression.There was no significant difference in the expressions of BAP1 and TET2 proteins between CMML-1 and CMML-2 patients(χ^2=0.40,P=0.53;χ^2=0.17,P=0.68).There was no significant difference in the expressions of BAP1 and TET2 proteins between CMML and AMML patients(χ^2=0.01,P=0.94;χ^2=0.36,P=0.64).There were significant differences in the positive expression rate of BAP1 and TET2 proteins between hematological neoplastic disease(CMML+AMML)and hematological non-neoplastic disease(IDA)(χ^2=6.01,P<0.05;χ^2=11.04,P<0.01).Pearson correlation analysis showed that there was no correlation between expressions of BAP1 and TET2 proteins(r=0.35,P=0.27).Univariate analysis showed that anemia(Hb<60 g/L),mature monocyte count≥2.0×10^9/L,neutrophil count(1.5×10^9/L),abnormal karyotype were associated with poor prognosis for CMML.Protein expressions of BAP1 and TET2 were not related with the prognosis of CMML(χ^2=0.28,P=0.600;χ^2=0.53,P=0.460).ConclusionBoth BAP1 and TET2 proteins have high positive expression rates in CMML patients,but the expressions of them are not related to the prognosis.