Xin He1, Wenlu Li2, Xiaogong Liang3, Xuan Zhu4, Lei Zhang1, Yu Huang5, Teng Yu1, Shu Li1, Zhigang Chen6,7. 1. Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2. Department of Pharmacy, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 3. Department of Hematology, Central Hospital of MianYang city, Mianyang, China. 4. Department of Surgical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 5. Department of Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, China. 6. Department of Surgical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Chinachenzhigang@zju.edu.cn. 7. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, Chinachenzhigang@zju.edu.cn.
Abstract
BACKGROUND/AIMS: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. METHODS: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AML patients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations. Meta-analysis was performed to evaluate the association of IGF2BP2 and prognosis. Lentivirus-based shRNAs were used to knock down IGF2BP2 in AML cell lines KG-1a and Kasumi. RESULTS: We searched the public database Gene Omnibus and analyzed IGF2BP2 expression in both AML and healthy populations. The results showed that IGF2BP2 was overexpressed in AML patients. To verify this phenomenon in fresh human samples, we compared the expression of IGF2BP2 in primary cells from 10 AML patients and 10 healthy controls and found that the expression of IGF2BP2 was upregulated in AML primary cells. More importantly, we observed that IGF2BP2 expression was negatively correlated with the CEBPA mutation status, which is an indicator of good prognosis (RR=0.648, p=0.0001). In addition, IGF2BP2 expression was positively associated with poor prognostic factors, such as the FLT3-ITD mutation (RR=1.198, p=0.0009) and IDH1 mutation (RR=1.354, p=0.0003), as well as intermediate and poor cytogenetic risk (RR=1.214, p=0.0026). To evaluate the prognostic value of IGF2BP2 in AML, we further performed a meta-analysis of 8 studies consisting of 1731 patients and found that IGF2BP2 overexpression was correlated with worse overall survival in AML patients [HR=1.31(1.16-1.49); p = 0.00]. Furthermore, we performed Gene Omnibus and Gene Set Enrichment analyses and found that the genes regulated by IGF2BP2 were mainly enriched in cell proliferation. IGF2BP2 knockdown by 4 different shRNA vectors significantly inhibited the growth of two AML cell lines, KG-1a and Kasumi. CONCLUSION: Thus, IGF2BP2 may serve as a biomarker to predict the prognosis of AML and as a potential target in AML.
BACKGROUND/AIMS: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. METHODS: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AMLpatients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations. Meta-analysis was performed to evaluate the association of IGF2BP2 and prognosis. Lentivirus-based shRNAs were used to knock down IGF2BP2 in AML cell lines KG-1a and Kasumi. RESULTS: We searched the public database Gene Omnibus and analyzed IGF2BP2 expression in both AML and healthy populations. The results showed that IGF2BP2 was overexpressed in AMLpatients. To verify this phenomenon in fresh human samples, we compared the expression of IGF2BP2 in primary cells from 10 AMLpatients and 10 healthy controls and found that the expression of IGF2BP2 was upregulated in AML primary cells. More importantly, we observed that IGF2BP2 expression was negatively correlated with the CEBPA mutation status, which is an indicator of good prognosis (RR=0.648, p=0.0001). In addition, IGF2BP2 expression was positively associated with poor prognostic factors, such as the FLT3-ITD mutation (RR=1.198, p=0.0009) and IDH1 mutation (RR=1.354, p=0.0003), as well as intermediate and poor cytogenetic risk (RR=1.214, p=0.0026). To evaluate the prognostic value of IGF2BP2 in AML, we further performed a meta-analysis of 8 studies consisting of 1731 patients and found that IGF2BP2 overexpression was correlated with worse overall survival in AMLpatients [HR=1.31(1.16-1.49); p = 0.00]. Furthermore, we performed Gene Omnibus and Gene Set Enrichment analyses and found that the genes regulated by IGF2BP2 were mainly enriched in cell proliferation. IGF2BP2 knockdown by 4 different shRNA vectors significantly inhibited the growth of two AML cell lines, KG-1a and Kasumi. CONCLUSION: Thus, IGF2BP2 may serve as a biomarker to predict the prognosis of AML and as a potential target in AML.
Authors: Yuanming Cheng; Wei Xie; Brian F Pickering; Karen L Chu; Angela M Savino; Xuejing Yang; Hanzhi Luo; Diu Tt Nguyen; Shanlan Mo; Ersilia Barin; Anthony Velleca; Thomas M Rohwetter; Dinshaw J Patel; Samie R Jaffrey; Michael G Kharas Journal: Cancer Cell Date: 2021-05-27 Impact factor: 38.585