白血病干/祖细胞相关基因表达在急性白血病中的临床意义  

Clinical Significance of Leukemia Stem/Progenitor Cell Related Gene Expression in Acute Leukemia

作　　者：朱海波[1,2] 赵明峰[1,2] 谢芳[1,2] 肖霞[1,2] 徐新女[3] 穆娟[1,2] 杨皎娃[1,2] 刘鹏江[1,2] 吕海容[1,2] 李玉明[1,2] 

机构地区：[1]天津医科大学第一中心临床学院 [2]天津市第一中心医院血液科,天津300192 [3]天津市第一中心医院卫生部急救医学重点实验室,天津300192

出　　处：《中国实验血液学杂志》2011年第5期1150-1155,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号81041043);教育部留学归国人员科研启动基金(编号教外司留[2007]1108);天津市卫生局科技基金(编号05KY10)

摘　　要：本研究旨在检测白血病干/祖细胞(LSPC)相关基因ABCB1、BMI-1、HOXB4在急性白血病患者骨髓中的表达,并探讨其在急性白血病中的临床意义。采集41例初治急性白血病患者的骨髓、16例缓解期患者的骨髓及10例非恶性血液病患者骨髓标本(作为对照)。采用SYBR Green相对定量RT-PCR法检测ABCB1、BMI-1、HOXB4基因的表达水平,并分析它们与急性白血病疗效、预后的关系。结果表明,ABCB1、BMI-1、HOXB4在对照组均无表达,在初治组相对表达量分别为4.26±2.26、3.72±1.91、3.74±2.38;而在缓解标本组分别为2.14±1.47、2.07±0.99、1.47±0.89,均明显低于初治组(p<0.05);正规化疗2个疗程内能够获得完全/部分缓解的患者的基因相对表达量分别为1.77±1.29、2.09±1.26、1.78±1.49,明显低于未缓解的难治病例(分别为7.23±1.78、3.96±0.92、4.48±2.57)(p<0.01)。单因素分析发现,各个基因高表达患者的白血病干/祖细胞免疫表型(CD34+CD38-CD96+和CD34+CD38-CD123+)表达阳性的比例及出现高白细胞(≥30×109/L)的几率均高于低表达患者,差异显著(p<0.05);而综合分析各个基因的表达,上述变化的p值均小于单因素分析p值,差异更显著(p<0.01)。结论:LSPC相关基因(ABCB1、BMI-1、HOXB4)表达与LSPC免疫表型呈相关性,在急性白血病患者发病初期表达增高,缓解后其表达水平明显下降;表达高者易出现高白细胞,化疗效果差,缓解率低。综合多指标分析可能是一种更好地临床评估疗效和预后的方法。This study was aimed to detect the expression of leukemia stem/progenitor cell（LSPC） related genes（ABCB1,BMI-1,HOXB4） in the patients with acute leukemia,and to explore its clinical significance in acute leukemia.Bone marrow samples were collected from de novo acute leukemia patients（41 cases）,patients with complete remission（CR,16 cases） and the patients with non-malignant hematologic diseases（10 cases） respectively.And the expressions of ABCB1,BMI-1,HOXB4 genes were detected by comparative real-time quantitative PCR（RQ-PCR） with SYBR Green assay.The results showed that the expressions of ABCB1,BMI-1,HOXB4 were not detected in the patients with non-malignant hematologic diseases,but were higher（relative expressive level： 4.26±2.26,3.72±1.91,3.74±2.38） in de novo acute leukemia patients and lower（relative expressive level： 2.14±1.47,2.07±0.99,1.47±0.89） in the acute leukemia patients with CR（p0.05）.The expressions of LSPC related genes were lower（relative expressive level： 1.77±1.29,2.09±1.26,1.78±1.49） in the patients acquired CR/partial remission（PR） than those in the patients not acquired CR/PR（relative expressive level： 7.23±1.78,3.96±0.92,4.48±2.57）（p0.01）.Unvariate analysis revealed that there were more cases with the expression of LSPC immunophenotype（CD34＋CD38-CD96＋ and CD34＋CD38-CD123＋） and more hyperleukocytosis cases in patients with any higher expression of LSPC related gene（p0.05）.Analysis of multiple parameters discovered larger significance（p0.01）.It is concluded that there is a good relationship between LSPC related genes（ABCB1,BMI-1,HOXB4） and LSPC immunophenotype.The expression of LSPC-related genes is higher in denovo acute leukemia patients,and lower in patients acquired CR/PR.The patients with higher expressed LSPC-relatedgenes display worse response to chemotherapy,lower CR/PR rate and higher leukocytosis,the analysis of multipleparameters may be a good method for assessing the therapeutic efficac

关 键 词：白血病干细胞 ABCBI BMI-1 HOXB4 急性白血病 

分 类 号：R733.71[医药卫生—肿瘤]