Rong Zhang,1 Cai-hong Huo2 1Department of Hematology, Xi’an Gaoxin Hospital, Xi’an 710065, People’s Republic of China; 2Department of Blood Transfusion, Yulin No.2 Hospital, Yulin 719000, People’s Republic of ChinaCorrespondence: Cai-hong HuoDepartment of Blood Transfusion, Yulin No.2 Hospital, Yulin 719000, People’s Republic of ChinaTel +8618992246809Email huocaihong@163.comBackground: LncRNAs play an important role in tumorigenesis and development in tumors, but the function of lncRNA SOCS2-AS in acute myeloid leukemia (AML) is unknown.Materials and Methods: In the present study, we used RT-PCR to detect the expression of SOCS2-AS in FLT3-ITD+, FLT3-ITD- AML patients and different AML cell lines. The colony formation and CCK-8 assay were performed to analyze the proliferation ability, and the flow cytometry was performed to analyze the capacity of apoptosis in Molm-13 and MV4-11 cells. The Western blot was applied to detect the expression of STAT5 and p-STAT5. The RNA pull-down and luciferase activity were used to investigate the interaction between SOCS2-AS and miR-221.Results: The results indicate that SOCS2-AS shows overexpression in FLT3-ITD+ AML patients compared to FLT3-ITD- AML patients. Si-SOCS2-AS can inhibit the proliferation, boost the apoptosis and induce the cycle arrest in Molm-13 cells, and SOCS2-AS overexpression promotes proliferation and colony formation in MV4-11 cells. The miR-221 shows overexpression in FLT3-ITD+ AML patients compared to FLT3-ITD- AML patients. And the expression level of miR-221 and SOCS2-AS shows negative correlation in FLT3-ITD+ AML patients. Functionally, SOCS2-AS could be interacted with miR-221 in AML cells. After SOCS2-AS knockdown, the phosphorylation level of STAT5 was significantly decreased. Moreover, miR-221 inhibitor can rescue the viability in cells after si-SOCS2-AS transfection. And it is stated that SOCS2-AS regulates the STAT5 signal transduction pathway with sponging miR-221.Conclusion: In conclusion, this study confirms the molecular mechanism of SOCS2-AS in AML by targeting the miR-221/STAT5 signaling pathway. This indicates SOCS2-AS may serve as a potential therapeutic target for the treatment of AML.Keywords: SOCS2-AS, acute myeloid leukemia, miR-221, FLT3-ITD+