A group led by Professor Hiroyuki Mano of the University of Tokyo Graduate School of Medicine elucidated the oncogenes responsible for about 65% of B-cell acute lymphoblastic leukemia, one of the most common cancers of the AYA generation. Announced that it was done.
The research group comprehensively analyzed 73 leukemia cells of AYA generation B-ALL patients using a next-generation sequencer, and found that some 65% of B-ALL patients had some kind of fused oncogene. bottom.Of these, the DUX4-IGH fusion gene, which is a completely new oncogene, was the most common (about 16%), the ZNF2 fusion gene was the second, and the novel MEF384D fusion gene was the third.
The association between the DUX4 gene and carcinogenesis has been unknown.However, according to this analysis, in AYA generation B-ALL, the DUX4 gene is inserted into the immunoglobulin gene H chain (IGH) locus and fused (translocated) after the posterior side is scraped, resulting in a large amount of DUX4-IGH fusion protein. Was revealed to be produced.This fusion protein has a strong carcinogenic potential, and when the DUX4-IGH fusion protein is produced in mouse B cells, the mouse develops leukemia, and in the B-ALL cell line carrying DUX4-IGH, DUX4- We also confirmed that reducing the expression of IGH induces cell death.In addition, DUX4-IGH exists specifically in the AYA generation, and detection cases were extremely rare in B-ALL in children and adults.Furthermore, leukemias with DUX4-IGH or ZNF384 fused oncogene belong to the good prognosis group (patients with long-term survival), and leukemias with MEF2D fused oncogenes have poor prognosis (patients with short survival). ) Also clarified that it belongs to.
In the future, the development of innovative therapies can be expected by suppressing the action of DUX4-IGH, and the fusion gene cluster containing DUX4-IGH will be a new prognostic biomarker.
