Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: Its correlation with FLT3
Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: Its correlation with FLT3
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DOI：
10.4149/neo_2013_085
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发表时间：
2013-01-01
期刊：
影响因子：
3
通讯作者：
Vora, H. H.
中科院分区：
文献类型：
--
作者：
Mehta, S. V.;Shukla, S. N.;Vora, H. H.
急性髓性白血病（AML）的潜在预后生物标志物可以通过了解白血病发生的细胞途径和分子变化来确定。细胞凋亡失调是AML的重要特征之一，为了了解细胞凋亡的分子机制及其对肿瘤进展的贡献，本研究旨在评估AML中抗凋亡Bcl2蛋白的表达及其与FLT3参数在疾病预后中的作用。用流式细胞术定量分析174例新发AML、骨髓增生异常综合征（MDS）和再生障碍性贫血患者白血病母细胞中Bcl2和FLT3蛋白的表达。采用PCR和RT-PCR方法对FLT3内部串联重复（ITD）、酪氨酸激酶结构域（TKD）点突变及mRNA水平进行定量分析。AML患者Bcl2阳性的发生率为71%。Bcl2阳性与CD34+和CD117+ AML显著相关。Bcl2阳性倾向于与DFS降低相关，而Bcl2阳性与FLT3蛋白阳性显著相关。在多变量分析中，Bcl2+和联合Bcl2+/FLT3蛋白+以及高WBC计数成为DFS降低的不良预后因素，高blast计数预测OS降低。在MDS患者中，Bcl2的表达率较高，而在再生障碍性贫血患者中，Bcl2的表达率较低。Bcl2和FLT3蛋白阳性患者的DFS显著降低，表明这些蛋白在白血病细胞的化疗耐药中起平行作用。
Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods.The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low.Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.