Research On The Role And Mechanism Of SENP1and MLL3in Acute Leukemia

Research on the role and mechanism of SENP1regulatingc-Myb in acute lymphoblastic leukemiaBackground and Objective:Acute lymphoblastic leukemia(ALL) is defined as a clonal malignant disease ofhematopoietic system,which is the first incidence of children with acute leukemia.Previousresearches revealed the relationship between occurrence of ALL and abnormal chromosomeand some genes, but mechanism of ALL is still unclear.Most of the researches focus onabnormality of chromosome, DNA and transcriptional level of genes. It was observed thatprotein post-translational modification played a significant role in occurrence anddevelopment of tumor.SUMOylation is an important method of post-translationalmodifications and de-SUMOylation in large amounts of protein are catalyzed bySUMO-specific protease1(SENP1) is associated with occurrence and development ofmultiple tumors. c-Myb is deemed to play a vital role in hematopoietic differentiation andtransformation. Our previous studies have found correlation between SENP1and highexpression of c-Myb in AML patients’ marrow while interaction sites of SENP1and c-Mybhave been detected. Thus we supposed that SENP1may mediate de-SUMOylation ofc-Myb to involve pathogenesis of ALL. In this work, we detected expression of SENP1andc-Myb in ALL marrow samples and their correlation were analyzed. This work providedclinical evidence for illuminating function, mechanism and relation with prognosis ofSENP1and c-Myb in ALL.Methods:Thirty-one diagnosed ALL patients were selected, in which one was T-ALL,twenty-two were B-ALL, and eight were unclassified ALL. Patients were divided intolow/intermediate risk and high risk groups, the number in which is6and25, respectively.The normal control group contains31people.We detected marrow samplesabout mRNA and relative protein expression of SENP1and c-Myb both in ALL groupandcontrol group.Results:we found high expression of SENP1and c-Myb in ALL marrow samples. There issignificant difference between ALL group and control group (p<0.05). Pearson correlationanalysis revealed positive correlation between SENP1and high expression of c-Myb.Expression of SENP1and c-Myb in high risk group was higher than that inlow/intermediate group, but there is no significant difference.Conclusion:High expression of SENP1and c-Myb in ALL marrow samples were detected andtheir positive correlation was analyzed, which may indicate that SENP1and c-Myb involveoccurrence and development of ALL. Exome sequencing identifies an MLL3gene germline mutationin a pedigree of colorectal cancer and acute myeloid leukemiaBackground and Object:We treated one patient with leukemia whose mutiple relatives were diagnosed withcancer. The propositus and his brother suffered from acute myeloid leukemia successively.And his mother, uncle and aunt were attacked by colon cancer, rectal cancer and rectalnecrosis, respectively. It was supposed that some genetic factors may result in occurrence ofmultiple patients with cancer. Therefore, we sequenced the whole exome of some membersin this family to identify relative genetic mutation.Methods:Marrow and peripheral blood specimen were collected from seven people in thisfamily for extracting DNA by genome-exome extraction kit. After detecting concentrationand quality of DNA with microplate reader and integrity with gel electrophoresis, DNAspecimen were taken to Beijing BerryGenomics Co.,Ltd.for whole exome sequencing.Results:There was insertion mutation of MLL3on7chromosome of several family members,which started from817to827codon in exon14, leading to a frame shift mutation of MLL3.Methylation of many tumor suppressor gene were also observed.Conclution:We found close relationship between MLL3and methylation after literature review.MLL3was related with generation and development of multiple tissue while mutation ofMLL3was connected with oncogenesis. Our study indicated there was significance andpotential prospect with anti-methylation and targeted therapy for MLL3mutation.