ArticleThe Journal of experimental medicine2014
Frequent disruption of the RB pathway in indolent follicular lymphoma suggests a new combination therapy.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities.Frontiers in immunology · 2023Review
- Advances in the multi-omics landscape of follicular lymphoma.International journal of biological sciences · 2023Review
- Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression.Blood cancer discovery · 2022Article
- Non-Hodgkin Lymphoma Metabolism.Advances in experimental medicine and biology · 2021Article
- Genomic studies indicate a novel combination therapy for follicular lymphoma.Molecular & cellular oncology · 2021Article
- Cyclin D3 Governs Clonal Expansion of Dark Zone Germinal Center B Cells.Cell reports · 2020Article
- The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.Nature cancer · 2020Article
- Follicular lymphoma.Nature reviews. Disease primers · 2019Review
- EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains.Nature genetics · 2019Article
- Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma.Blood · 2018Article
- Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.Nature cell biology · 2017Article
- Genetic and epigenetic inactivation ofScience translational medicine · 2017Article
- Murine models of germinal center derived-lymphomas.Current opinion in immunology · 2017Review
- Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Article
- Concomitant inactivation of the p53- and pRB- functional pathways predicts resistance to DNA damaging drugs in breast cancer in vivo.Molecular oncology · 2015Article
- Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1.Leukemia · 2015Article
- Man's best friend: what can pet dogs teach us about non-Hodgkin's lymphoma?Immunological reviews · 2015Review
- Longitudinal drug synergy assessment using convolutional neural network image-decoding of glioblastoma single-spheroid cultures.Neuro-oncology advancesArticle
- Non-Hodgkin Lymphoma Metabolism.Advances in experimental medicine and biologyReview
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Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
Abstract
Loss of cell cycle controls is a hallmark of cancer and has a well-established role in aggressive B cell malignancies. However, the role of such lesions in indolent follicular lymphoma (FL) is unclear and individual lesions have been observed with low frequency. By analyzing genomic data from two large cohorts of indolent FLs, we identify a pattern of mutually exclusive (P = 0.003) genomic lesions that impair the retinoblastoma (RB) pathway in nearly 50% of FLs. These alterations include homozygous and heterozygous deletions of the p16/CDKN2a/b (7%) and RB1 (12%) loci, and more frequent gains of chromosome 12 that include CDK4 (29%). These aberrations are associated with high-risk disease by the FL prognostic index (FLIPI), and studies in a murine FL model confirm their pathogenic role in indolent FL. Increased CDK4 kinase activity toward RB1 is readily measured in tumor samples and indicates an opportunity for CDK4 inhibition. We find that dual CDK4 and BCL2 inhibitor treatment is safe and effective against available models of FL. In summary, frequent RB pathway lesions in indolent, high-risk FLs indicate an untapped therapeutic opportunity.
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