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High bone marrow ID2 expression predicts poor chemotherapy response and prognosis in acute myeloid leukemia

机译:骨髓ID2高表达预示急性髓细胞白血病的化疗反应不良和预后不良

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摘要

Dysregulation of ID proteins is a frequent event in various human cancers and has a direct role in cancer initiation, maintenance, progression and drug resistance. Our previous study has revealed ID1 expression and its prognostic value in acute myeloid leukemia (AML). Herein, we further reported ID2 expression and its clinical significance in AML. Real-time quantitative PCR was performed to detect ID2 transcript level in bone marrow mononuclear cells of 145 de novo AML patients. ID2 expression was significantly up-regulated in AML patients compared with controls. ID2 overexpression occurred with the highest frequency in poor karyotype (10/17, 59%), lower in intermediate karyotype (35/83, 42%), and the lowest in favorable karyotype (7/40, 18%). Moreover, high ID2 expression correlated with lower complete remission (CR) rate, shorter overall survival, and acted as an independent prognostic biomarker in whole-cohort AML and non-M3-AML patients. Importantly, the prognostic value of ID2 expression in AML was validated by The Cancer Genome Atlas (TCGA) data. In the follow-up of patients, ID2 expression at CR phase was decreased than at the time of diagnosis, and was increased again at the time of relapse. These findings demonstrated that bone marrow ID2 overexpression was a frequent event in AML patients, and predicts poor chemotherapy response and prognosis.
机译:ID蛋白的失调在各种人类癌症中是经常发生的事件,并且在癌症的发生,维持,进展和耐药性中具有直接作用。我们先前的研究揭示了ID1在急性髓细胞性白血病(AML)中的表达及其预后价值。在本文中,我们进一步报道了ID2在AML中的表达及其临床意义。实时定量PCR检测了145名新生AML患者的骨髓单个核细胞中的ID2转录水平。与对照组相比,AML患者中的ID2表达明显上调。 ID2过表达的发生频率在不良核型中最高(10 / 17,59%),在中等核型中较低(35 / 83,42%),在有利核型中最低(7 / 40,18%)。此外,高ID2表达与较低的完全缓解(CR)率,较短的总生存期有关,并且在全队列AML和非M3-AML患者中充当独立的预后生物标志物。重要的是,通过癌症基因组图谱(TCGA)数据验证了ID2表达在AML中的预后价值。在患者的随访中,CR期的ID2表达低于诊断时,复发时再次升高。这些发现表明,骨髓ID2过度表达是AML患者中的常见事件,并预示着不良的化疗反应和预后。

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