Journal article
FOXM1 is a therapeutic target for high-risk multiple myeloma
Leukemia, Vol.30(4), pp.873-882
04/2016
DOI: 10.1038/leu.2015.334
PMCID: PMC4826574
PMID: 26648534
Abstract
The transcription factor forkhead box M1 (FOXM1) is a validated oncoprotein in solid cancers, but its role in malignant plasma cell tumors such as multiple myeloma (MM) is unknown. We analyzed publicly available MM datasets and found that overexpression of
FOXM1
prognosticates inferior outcome in a subset (~15%) of newly diagnosed cases, particularly patients with high-risk disease based on global gene expression changes. Follow-up studies using human myeloma cell lines (HMCLs) as the principal experimental model system demonstrated that enforced expression of FOXM1 increased growth, survival and clonogenicity of myeloma cells, whereas knockdown of FOXM1 abolished these features. In agreement with that, constitutive up-regulation of FOXM1 promoted HMCL xenografts in laboratory mice, whereas inducible knockdown of FOXM1 led to growth inhibition. Expression of cyclin dependent kinase 6 (CDK6) and NIMA-related kinase 2 (NEK2) was co-regulated with FOXM1 in both HMCLs and myeloma patient samples, suggesting interaction of these 3 genes in a genetic network that may lend itself to targeting with small-drug inhibitors for new approaches to myeloma therapy and prevention. These results establish
FOXM1
as high-risk myeloma gene and provide support for the design and testing of FOXM1-targeted therapies specifically for the FOXM1
High
subset of myeloma.
Details
- Title: Subtitle
- FOXM1 is a therapeutic target for high-risk multiple myeloma
- Creators
- Chunyan Gu - Basic Medical College, Nanjing University of Chinese Medicine, 210046 Nanjing, People’s Republic of ChinaYe Yang - Basic Medical College, Nanjing University of Chinese Medicine, 210046 Nanjing, People’s Republic of ChinaRamakrishna Sompallae - Basic Medical College, Nanjing University of Chinese Medicine, 210046 Nanjing, People’s Republic of ChinaHongwei Xu - Department of Internal Medicine, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242 Iowa, USAVan S Tompkins - Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242 Iowa, USACarol Holman - Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242 Iowa, USADirk Hose - Medizinische Klinik V, Universitätsklinikum HeidelbergHartmut Goldschmidt - Medizinische Klinik V, Universitätsklinikum HeidelbergGuido Tricot - Department of Internal Medicine, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242 Iowa, USAFenghuang Zhan - Department of Internal Medicine, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242 Iowa, USASiegfried Janz - Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242 Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Leukemia, Vol.30(4), pp.873-882
- DOI
- 10.1038/leu.2015.334
- PMID
- 26648534
- PMCID
- PMC4826574
- NLM abbreviation
- Leukemia
- ISSN
- 0887-6924
- eISSN
- 1476-5551
- Language
- English
- Date published
- 04/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984047785102771
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