BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2.

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2.
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BCL3 表达是 FAB 亚型 M2 急性髓系白血病的潜在预后和预测生物标志物

DOI:
10.1007/s12253-018-0476-7
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发表时间:
2019-04
期刊:
Pathology oncology research : POR
影响因子:
--
通讯作者:
Wang H
Wang H
中科院分区:
其他
文献类型:
--
作者:
Niu Y;Yang X;Chen Y;Zhang L;Jin X;Tang Y;Li L;Yu L;Guo Y;Wang H

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尽管BCL 3在人类慢性淋巴细胞白血病以及其他实体瘤中的意义已被披露,但BCL 3在急性髓系白血病(AML)中的表达的诊断和预后仍然很不清楚。在这项研究中,我们从101例初治AML患者和27例健康供体的骨髓单个核细胞中分离总RNA。结果AML患者BMMCs中BCL 3 mRNA表达水平明显低于正常对照组(P= 0.0015),AML低危核型患者BCL 3 mRNA表达水平高于中危核型患者(P= 0.014)。ROC分析表明BCL 3能有效区分AML患者和正常对照。在法美英(FAB)亚型中,M2亚型中BCL 3低表达的频率显著高于其他亚型M1/M4/M5/M6/M7(P= 0.006),而M4/M5亚型中BCL 3低表达的频率略低于M1/M2/M6/M7亚型(P= 0.064)。染色体分析显示,BCL 3低表达组t(8;21)异常率显著高于BCL 3高表达组(P= 0.0047),正常核型率显著低于BCL 3高表达组(P= 0.0059); BCL 3高表达组FLT 3-ITD突变率显著高于BCL 3低表达组(P = 0.028),C-Kit突变率显著低于BCL 3低表达组(P= 0.0232)。BCL 3低表达组和BCL 3高表达组的完全缓解率和总生存率无显著差异,但M2 AML中BCL 3高表达组的总生存率(OS,P= 0.049)、无复发生存率(RFS,P= 0.027)和无病生存率(DFS,P= 0.042)均显著低于BCL 3低表达组。M2亚型AML患者中,BCL 3高表达组的二次诱导治疗后完全缓解(CR)率明显低于BCL 3低表达组(P= 0.0317)。因此,这些研究结果表明,BCL 3似乎是一个有前途的分子生物标志物的儿童急性髓细胞白血病的预后不良。
Although the implication ofBCL3has been disclosed in human chronic lymphocytic leukemia as well as other solid tumors, the diagnostic and prognostic ofBCL3expression in acute myeloid leukemia (AML) remains largely unclear. In this study, we isolated total RNA from bone marrow mononuclear cells collected from 101 de novo AML patients and 27 healthy donors. After reverse transcription, quantitative real-time PCR was performed to detectBCL3expression level.BCL3mRNA level was significantly down-regulated in BMMCs of AML patients compared with healthy controls (P= 0.0015).BCL3was showed a higher level in AML patients with poor-risk karyotypes than that of in patients with favorable/intermediate-risk karyotypes (P= 0.014). ROC analysis demonstrated thatBCL3could effectively differentiate AML patients from normal controls. Among the French-American-British (FAB) subtypes, the frequency of lowBCL3expression in M2 subtypes is significantly higher than that of in the other subtypes M1/M4/M5/M6/M7 (P= 0.006), and mildly lower in myelomonocytic/monocytic subtypes M4/M5 (P= 0.064) than those in M1/M2/M6/M7 subtypes. Chromosome analysis revealed thatBCL3lowpatients had a remarkably higher frequency of t (8;21) abnormality (P= 0.0047) and lower frequency of normal karyotype (P= 0.0059) thanBCL3highpatients.BCL3highpatients showed a significantly higher frequency of FLT3-ITD mutation (P= 0.028) and lower frequency of C-Kit mutation (P= 0.0232) thanBCL3lowpatients. Although there were no significant differences in complete remission and overall survival between BCL3lowand BCL3highgroups, patients with high BCL3 expression markedly shorter overall survival (OS,P= 0.049), relapse-free survival (RFS,P= 0.027) and disease-free survival (DFS,P= 0.042) in M2 AML than low BCL3 expression patients. Additionally, in AMLs of M2 subtype, high BCL3 expression patients had markedly lower complete remission (CR) rate (P= 0.0317) after the second induction treatment than patients with BCL3 low expression. Thus, these findings indicated that BCL3 appeared as a promising molecular biomarker of pediatric acute myeloid leukemia with unfavorable prognosis.
DOI: 10.18632/oncotarget.12631
发表时间: 2016-12-13
期刊: Oncotarget
影响因子: --
作者:
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