Study on the application of human small brain organs in myeloma

Myeloma (MB) is a common malignant brain tumor in children with high invasiveness, morbidity and mortality.
has heterogeneity in biological characteristics and clinical manifestations, and can generally be divided into subtypes, of which the 3rd type MB children characterized by c-MYC increase have the worst prognosis, about 50% of the children have metastasis at the time of diagnosis.
currently, MB treatment options include maximum safe excision and full brain total spinal cord radiotherapy and chemotherapy for children aged ≥3, but with poor results.
, according to the genetic characteristics of patients, the establishment of humanized mouse MB model plays an important role in identifying and testing new drugs.
Claudio Ballabio of the Armenian-Harvard Brain Cancer Laboratory at the University of Trento in Italy screened the drive genes of type 3 MB, modeled human-induced cervical organs, and imported different gene-induced MBs for validation; the results were published online in January 2020 in Nature Communications.
the researchers first compared type 3 MB with normal small brains in the database, analyzed genes that differed more than 16 times, and then identified the driving genes of type 3 MB from Otx2 and c-MYC.
also developed a live trans-dyeing system that successfully induced MB tumors by over-expression of Gfi1-c-MYC (GM) and Otx2-c-MYC (OM) in mouse brains.
analysis for further search for therapeutic targets, the authors found that SMARCA4 mutation frequency was highest in type 3 MB of Otx2 and c-MYC over-expression.
and in mouse models, low expression of type 3 MB endo-origin SMARCA4 induced by Otx2/c-MYC was observed, but OTx2/c-MYC and SMARCA4 were found not to form MB in mice at the same time.
SMARCA4 inhibits Otx2/c-MYC induction to form type 3 MB, and mutant SMARCA4 inhibits the function of wild SMARCA4.
the above results fully show that the SMARCA4 mutation plays an important role in the occurrence of type 3 MB.
the authors successfully built a type 3 MB model in mice using different genetic combinations to trans-infect human brain organs.
SMARCA4 and EZH2 in the PRC2 complex, EZH2 inhibitors are expected to be a targeted drug for the treatment of type 3 MB.
in mouse animal models and organoids, EZH2 inhibitors can significantly induce type 3 MB apoptosis, so it is expected to become a clinical treatment type 3 MB drug.
Results The results show that human cer cerebral organs can be used in the exploration of MB tumor occurrence mechanism, in-depth understanding of the role of tumor-driven gene mutations, and become a tool for the development of individualized treatment of MB patients.
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