The Effect Of Rip1, Rip3, Sirt2 On The Development Of MLL Leukemia Was Identified Using RNA-Seq

MLL fusion protein is frequently found in the AML and ALL patients,and these patients consistently have a poor progonosis.MLL-AF9 and MLL-ENL are the two most common MLL fusion proteins.We hope to find the precision targets of these two kinds of fusion gene leukemia.Based on our previous research,we choose Rip1,Rip3,Sirt2 as our objects to carry out further research;Rip1 and Rip3 are two important genes in the cell fate decision,they involved in the process of cell death and survival;Sirt2 is a deacetylation cytokine,it can promote the cell necroptosis pathway.We choose the cell lines which were induced by MLL-ENL and MLL-AF9 to research the influences of Rip1,Rip3,Sirt2 on the development and progression of leukemia cells.We had found that depletion of Rip1 and Rip3 can supress the development of leukemia and depletion of Sirt2 can enhance the survival of leukemia.What’s more,depletion of Rip1 has more significant influence on leukemias than depletion of Rip3.Through RNA-seq,the expression levels of intracellular gene can be revealed,and the expression differences of each pathway can be understood,thus providing an explanation for our understanding of cell process.After the transcriptome sequencing of six cell lines(MLL-AF9WT,MLL-AF9-Rip1^-/-,MLL-AF9-Rip3^-/-,MLL-AF9-Sirt2^-/-,MLL-ENL-WT,MLL-ENL-Sirt2^-/-),we found that compared with Rip3 knockout mice,in Rip1 knockout mice,tumer necrosis factor mediat signaling pathway、extrinsic apoptic signaling pathway、myloid cell diffrentiation pathway、regulation hemopoisis pathway have gretaly changed,suggest that the more weak Ripk1knock out cell line is due to these changed pathways.In Sirt2 depletion cell lines,we found that the MLL-ENL-Sirt2^-/-response to hormone stimulus pathway and regulate of cell death pathway are much more up-regulate than MLL-ENL-WT,suggest that the phenomenon observed in MLL-ENL-Sirt2^-/-leukemia may be caused by the diffrent influnce of Sirt2 on these pathway.By transcriptome sequencing,we provide a general direction for our next experiment.For understanding Rip1 and Rip3,Sirt2 is of great significance for the understanding of fusion-gene leukemia.