WDR26 and MTF2 are therapeutic targets in multiple myeloma

Fumou Sun; Yan Cheng; Jesse D Riordan; Adam Dupuy; Wendy Dubois; Michael Pisano; Jing Dong; Beverly Mock; Fenghuang Zhan; Parameswaran Hari; Siegfried Janz

doi:10.1186/s13045-021-01217-9

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WDR26 and MTF2 are therapeutic targets in multiple myeloma

Journal article

Open access

Peer reviewed

WDR26 and MTF2 are therapeutic targets in multiple myeloma

Fumou Sun, Yan Cheng, Jesse D Riordan, Adam Dupuy, Wendy Dubois, Michael Pisano, Jing Dong, Beverly Mock, Fenghuang Zhan, Parameswaran Hari, …

Journal of hematology and oncology, Vol.14(1), pp.203-203

12/07/2021

DOI: 10.1186/s13045-021-01217-9

PMCID: PMC8650373

PMID: 34876184

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https://doi.org/10.1186/s13045-021-01217-9View

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Abstract

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.

Adaptor Proteins, Signal Transducing - genetics

Animals

Gene Expression Regulation, Neoplastic

Humans

Mice

Mice, Transgenic

Multiple Myeloma - genetics

Multiple Myeloma - therapy

Polycomb Repressive Complex 2 - genetics

Details

Title: Subtitle: WDR26 and MTF2 are therapeutic targets in multiple myeloma
Creators: Fumou Sun - Medical College of Wisconsin
Yan Cheng - Medical College of Wisconsin
Jesse D Riordan - University of Iowa
Adam Dupuy - University of Iowa
Wendy Dubois - Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Michael Pisano - Medical College of Wisconsin
Jing Dong - Medical College of Wisconsin
Beverly Mock - Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Fenghuang Zhan - University of Arkansas for Medical Sciences
Parameswaran Hari - Medical College of Wisconsin
Siegfried Janz - Medical College of Wisconsin
Resource Type: Journal article
Publication Details: Journal of hematology and oncology, Vol.14(1), pp.203-203
DOI: 10.1186/s13045-021-01217-9
PMID: 34876184
PMCID: PMC8650373
NLM abbreviation: J Hematol Oncol
ISSN: 1756-8722
eISSN: 1756-8722
Grant note: R01CA236814 / NCI NIH HHS R01 CA151354 / NCI NIH HHS R01CA151354 / NCI NIH HHS CA180190 / NIH HHS
Language: English
Date published: 12/07/2021
Academic Unit: Anatomy and Cell Biology; Pathology; Internal Medicine
Record Identifier: 9984284448802771

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