Implications of the miR-10 family in chemotherapy response of NPM1-mutated AML
Implications of the miR-10 family in chemotherapy response of NPM1-mutated AML
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DOI：
10.1182/blood-2013-10-532374
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发表时间：
2014-04-10
期刊：
影响因子：
20.3
通讯作者：
Garzon, Ramiro
中科院分区：
文献类型：
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作者：
Havelange, Violaine;Ranganathan, Parvathi;Garzon, Ramiro
核磷蛋白突变的急性髓系白血病（NPM1mut-AML）患者诱导化疗的完全缓解（CR）率很高。然而，造成这种影响的机制尚不清楚。由于 miR-10 家族成员在 NPM1mut-AML 中高水平表达，我们评估了这些 microRNA 是否可以预测 AML 中的化疗反应。我们发现 54 名未经治疗的细胞遗传学异质性 AML 患者中 miR-10 家族基线高表达与达到 CR 相关。然而，当我们将 NPM1 突变状态纳入多变量模型时，miR-10a-5p 表达与 NPM1 突变状态之间存在显着的交互作用。当使用由 183 名细胞遗传学正常的老年（年龄 >= 60 岁）AML 患者组成的第二组时，也观察到了类似的结果。在细胞系和原代母细胞中使用 miR-10a-5p 进行的功能丧失和功能获得实验并未显示出对基线或化疗后细胞凋亡或细胞增殖有任何影响。这些数据支持 miR-10 家族在 NPM1mut-AML 中的旁观者角色。
Nucleophosmin-mutated acute myeloid leukemia (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. BecausemiR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs could predict chemotherapy response in AML. We found that high baseline miR-10 family expression in 54 untreated cytogenetically heterogeneous AML patients was associated with achieving CR. However, when we included NPM1 mutation status in the multivariable model, there was a significant interaction effect between miR-10a-5p expression and NPM1 mutation status. Similar results were observed when using a second cohort of 183 cytogenetically normal older (age >= 60 years) AML patients. Loss-and gain-of-function experiments using miR-10a-5p in cell lines and primary blasts did not demonstrate any effect in apoptosis or cell proliferation at baseline or after chemotherapy. These data support a bystander role for the miR-10 family in NPM1mut-AML.