Molecular Cloning And Functional Study Of The Fusion Gene By The Chromosome Translocation T(3;11) (q29q13;p15) In A Hybrid Acute Leukemia Patient

ObjectiveLeukemia is a kind of malignant tumor of hematopoietic system doing severely harm to human health, always with non-random cytogenetic abnormalities, among which the most frequency is chromosomal translocation. It can be seen in 65% acute leukemia patients. Mostly targed genes of chromosomal translocation are transcriptional factor or trosine-protein kinase, resulting in dysregulative pathwalys of cell proliferation, apoptosis, differentiation and playing an important role in leukemogenesis. Therefore, detection of the recurrent chromosomal translocations, molecular cloning and functional study of the involved genes will shed light on deciphering the molecular mechanisms of leukemogenesis, provide diagnostic markers and allow the development of new therapeutic strategies. In recent years, chromosome aberration involving 11p15 has been reported increasingly. To date at least 17 kinds have been identified. Almost all 11p15 translocations targed the NUP98 gene located at chromosome 11p15. Our work is to provide considerable insight into the mechanisms of NUP98-related fusion genes in leukemia through molecular cloning and functional study of the fusion genes by the chromosome translocation t(3;11)(q29q13;p15) in a hybrid acute leukemia patient Furthermore,it will help to diagnose, guide risk-directed therapy for leukemia.MethodsWe investigated an adult patient with the chromosome translocation t(3;11)(q29q13;p15) in de novo hybrid acute leukemia. With positional candidate gene approaches, we characterized the genes involved in that translocation and subsequently studied the function of the fusion protein in leukemogenic mechanism.Part I: Firstly, through molecular genetic-cytogenetics, we identified a new chromosomal translocation t(3;11)( q13;p15) and located chromosome breakpoint at the NUP98 gene at 11p15. Using Rapid Amplification of cDNA Ends (RACE), we...