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与B急性淋巴细胞白血病预后相关的差异表达基因的鉴定

Identification of differentially expressed genes associated with prognosis of B acute lymphoblastic leukemia.

作者信息

Garza-Veloz Idalia, Martinez-Fierro Margarita L, Jaime-Perez Jose Carlos, Carrillo-Sanchez Karol, Ramos-Del Hoyo Maria Guadalupe, Lugo-Trampe Angel, Rojas-Martinez Augusto, Gutierrez-Aguirre Cesar Homero, Gonzalez-Llano Oscar, Salazar-Riojas Rosario, Hidalgo-Miranda Alfredo, Gomez-Almaguer David, Ortiz-Lopez Rocio

机构信息

Departamento de Bioquimica y Medicina Molecular, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Avenida F. I. Madero, S/N, Col. Mitras Centro, 64460 Monterrey, NL, Mexico ; Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas, Carretera Zacatecas-Guadalajara Km 6, 98160 Ejido la Escondida, ZAC, Mexico.

Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas, Carretera Zacatecas-Guadalajara Km 6, 98160 Ejido la Escondida, ZAC, Mexico.

出版信息

Dis Markers. 2015;2015:828145. doi: 10.1155/2015/828145. Epub 2015 Feb 24.

Abstract

BACKGROUND

Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL.

METHODS

219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction.

RESULTS

Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73-27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05).

CONCLUSIONS

Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

摘要

背景

B型急性淋巴细胞白血病(B-ALL)是一种死亡率很高的肿瘤性疾病。本研究的目的是验证与白血病相关信号通路有关的45个基因的表达谱,并评估它们与B-ALL预后的相关性。

方法

对73例B-ALL患者在诊断时、开始治疗后4周和8周获取的219份外周血单个核细胞样本进行研究。通过定量实时聚合酶链反应分析基因表达。

结果

23个基因的标准化ΔCq值在诊断时显示B-ALL与对照组之间存在差异(P值<0.05)。在至少一个评估时间点,B-ALL患者复发/死亡与IL2RA、SORT1、DEFA1和FLT3基因的表达水平之间存在显著关联(P值<0.05,比值比范围:3.73-27)。在研究的各个时间点,FLT3失调与复发/死亡之间的关联是持续存在的,其过表达在研究人群中显著增加了复发/死亡的几率,范围在3.73至6.05之间(P值<0.05)。

结论

FLT3和DEFA1基因的过表达对B-ALL的预后具有独立的预后意义,表现为研究人群中复发/死亡风险增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/621b/4354728/c038cacb5f5b/DM2015-828145.001.jpg

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