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Modeling Bone Cancer with Induced Pluripotent Stem Cells

Drs. Dung-Fang Lee and Ihor Lemischka at The Black Family Stem Cell Institute in Icahn School of Medicine at Mount Sinai recently reported in the journal Cell that they have successfully established induced pluripotent stem cells (iPSCs) from a rare genetic disease Li-Fraumeni syndrome (LFS) family and investigated the role of mutant p53, commonly known as the tumor suppressor, in the development of osteosarcoma. Osteosarcoma is the most common type of bone cancer in all children, and after leukemia, the second leading cause of cancer death for them. Their study revealed that the expression of genes enriched in LFS-derived bone cells strongly correlated with decreased time to tumor recurrence and poor patient survival. Furthermore, LFS-derived bone cells showed impaired expression of the imprinted gene H19 during osteogenesis. When normal H19 expression was restored, osteoblastic differentiation was facilitated in LFS-derived bone cells and tumorigenic potential was repressed. In summary, their work has implications for the future treatment or prevention of LFS-associated osteosarcoma, and possibly for all forms of bone cancer driven by p53 mutations, with H19 and p53 identified as potential targets for future drugs. This research was supported by NYSTEM awards, C024176 and C024410, to Dr. Lemischka.


Lee DF, Su J, Kim HS, Chang B, Papatsenko D, Zhao R, Yuan Y, Gingold J, Xia W, Darr H, Mirzayans R, Hung MC, Schaniel C, Lemischka IR. Modeling familial cancer with induced pluripotent stem cells. Cell. 2015 Apr 9;161(2):240-54.