The human nucleophosmin 1 mutation A inhibits myeloid differentiation of leukemia cells by modulating miR-10b
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Qin Zou1, Shi Tan2, Zailin Yang3, Juan Wang4, Jingrong Xian1, Shuaishuai Zhang1, Hongjun Jin1, Liyuan Yang1, Lu Wang1, Ling Zhang1
1Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
2Department of Clinical Laboratory, Chongqing Health Center for Women and Children, Chongqing, China
3Center for Hematology, Southwest Hospital, Third Military Medical University, Chongqing, China
4Children’s Medical Laboratory Diagnosis Center, Qilu Children’s Hospital of Shandong University, Jinan, China
Ling Zhang, email: [email protected]
Keywords: nucleophosmin 1, mutation, microRNA, leukemia, differentiation
Received: May 30, 2016 Accepted: September 16, 2016 Published: September 23, 2016
Mutations in the nucleophosmin 1 (NPM1) gene are the most frequent genetic alteration in acute myeloid leukemia (AML). Here, we showed that enforced expression of NPM1 mutation type A (NPM1-mA) inhibits myeloid differentiation of leukemia cells, whereas knockdown of NPM1-mA has the opposite effect. Our analyses of normal karyotype AML samples from The Cancer Genome Atlas (TCGA) dataset revealed that miR-10b is commonly overexpressed in NPM1-mutated AMLs. We also found high expression of miR-10b in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells. In addition, NPM1-mA knockdown enhanced myeloid differentiation, while induced expression of miR-10b reversed this effect. Finally, we showed that KLF4 is downregulated in NPM1-mutated AMLs. These results demonstrated that miR-10b exerts its effects by repressing the translation of KLF4 and that NPM1-mA inhibits myeloid differentiation through the miR-10b/KLF4 axis. This sheds new light on the effect of NPM1 mutations’ on leukemogenesis.
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