WDR26 and MTF2 are therapeutic targets in multiple myeloma. J Hematol Oncol 2021 Dec 07;14(1):203
Date
12/09/2021Pubmed ID
34876184Pubmed Central ID
PMC8650373DOI
10.1186/s13045-021-01217-9Scopus ID
2-s2.0-85120899924 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Unbiased genetic forward screening using retroviral insertional mutagenesis in a genetically engineered mouse model of human multiple myeloma may further our understanding of the genetic pathways that govern neoplastic plasma cell development. To evaluate this hypothesis, we performed a tumor induction study in MYC-transgenic mice infected as neonates with the Moloney-derived murine leukemia virus, MOL4070LTR. Next-generation DNA sequencing of proviral genomic integration sites yielded rank-ordered candidate tumor progression genes that accelerated plasma cell neoplasia in mice. Rigorous clinical and biological validation of these genes led to the discovery of two novel myeloma genes: WDR26 (WD repeat-containing protein 26) and MTF2 (metal response element binding transcription factor 2). WDR26, a core component of the carboxy-terminal to LisH (CTLH) complex, is overexpressed or mutated in solid cancers. MTF2, an ancillary subunit of the polycomb repressive complex 2 (PRC2), is a close functional relative of PHD finger protein 19 (PHF19) which is currently emerging as an important driver of myeloma. These findings underline the utility of genetic forward screens in mice for uncovering novel blood cancer genes and suggest that WDR26-CTLH and MTF2-PRC2 are promising molecular targets for new approaches to myeloma treatment and prevention.
Author List
Sun F, Cheng Y, Riordan JD, Dupuy A, Dubois W, Pisano M, Dong J, Mock B, Zhan F, Hari P, Janz SAuthors
Jing Dong PhD Assistant Professor in the Medicine department at Medical College of WisconsinParameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Transgenic
Multiple Myeloma
Polycomb Repressive Complex 2
