Function of OTUD7B in acute myeloid leukemia cells and its mechanism / 上海交通大学学报（医学版）

ABSTRACT

Objective·To investigate the biological effect and mechanism of OTUD7B in acute myeloid leukemia (AML) cells.Methods·The expression of OTUD7B in peripheral blood mononuclear cells and bone marrow mononuclear cells of AML patients were detected.The relationship between OTUD7B and survival of AML patients was confirmed by using TCGA database.Mouse model of M2 type AML was established,and the expression of OTUD7B in the bone marrow,spleen and liver of the mice was detected.OTUD7B was overexpressed in AML cell lines HL60 and kasumil,then the cell viability and cell cycle were measured.The AKT/mTOR pathway proteins were detected after OTUD7B overexpressed and then the cell growth inhibition was detected after overexpression ofAKT1.Results·The expression of OTUD7B was lower in primary leukemia cells from all types of AML patients and in the bone marrow,liver and spleen of M2 type AML mice,which was closely related to the survival time of AML patients.OTUD7B overexpression in HL60 and kasumil cells significantly inhibited the cell viability and decreased the percentage of S phase cells.OTUD7B significantly inhibited the phosphorylation of AKT and mTOR,and AKT1 overexpression partially reversed the inhibitory effect of OTUD7B on cell growth.Conclusion·OTUD7B expression is low in primary leukemia ceils from AML patients and in bone marrow,liver and spleen of the M2 type AML mice.The survival time of patients with low OTUD7B expression is shorter.Overexpression of OTUD7B significantly inhibited the cell viability of HL60 and kasumi 1 cells and the entry of cells into S phase.The inhibitory effect of OTUD7B overexpression on AML cells might be related to the inhibition ofAKT / mTOR signaling pathway.