The Preliminary Research About The Function Of Jab1/CSN5 In Acute Myeloid Leukemia

Acute myeloid leukemia(AML)is a malignant disease characterized by proliferation and maturation arrest of myeloid blasts in bone marrow and blood.The genetic abnormalities confer the leukemic clones with unlimited self-renewal and blockage of differentiation at the specific stage of development.Jab1/CSN5(c-Jun activation domain-binding protein-1)has been identified as one components of COP signal complex.Notably,alternations in the protein levels of Jabl/CSN5 have been observed in several types of cancers[3,10-14].In 2013,our laboratory has reported that Jabl,as a component of Smurf 1/2 E3 ligases,promotes Smad7 degradation and has been involved with differentiation[15].[Research Objective]The present study aimed to identify the specific expression level and functions of Jab1/CSN5 associated with AML[Research Methods]1)Immunohistochemistry experiments to detect Jabl/CSN5 expression in the bone marrow samples.2)The bone marrow samples were separated into granulocytes and lymphocytes.3)Western-blotting experiments demonstrated that Jab1/CSN5 was mainly expressed in the granulocyte cells.4)To increase Jab1/CSN5 expression,we used lentiviral particles packing Jab1 to infect cells.On the other hand,to knock down Jabl/CSN5 expression we used lentiviral particles packing shRNA expression vectors to infect cells.5)BrdU assay and the cellular CD11b,CD13,CD14 and CD15 were detected by the flow cytometry.[Results and Conclusions]To accomplish,we applied immunohistochemistry techniques to observe the elevated Jab1/CSN5 levels in AML patients' bone marrow samples.Furthermore,we separated and collected the granulocyte cells and lymphocyte cells from the bone marrow samples,respectively.The Western-blotting results demonstrated that Jab1/CSN5 was mainly expressed in the granulocyte cells.Moreover,Jabl/CSN5 promoted the proliferation and decreased the differentiation in K562,U937 and HL60 cell lines.Taken together,our findings demonstrated that Jabl promoted the proliferation and inhibited the differentiation and might reveal insights into the pathogenesis of AML.