Identifying the angiogenic receptor expression in mantle cell lymphoma patients and murine models

Mantle Cell Lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma, with frequent relapses and shorter responses with every subsequent treatment. MCL depends on growth factors and cytokines derived from microenvironmental cells for its growth and can alter the immune system to evade recognition and subsequent elimination. The soluble factors secreted by MCL can contribute to endothelial differentiation, lymphangiogenesis, and clonal selection under hypoxic conditions, thereby evading the DNA damage response. Targeting the tumor microenvironment and angiogenesis is an active area of research and development, as the angiogenic gene signatures in MCL remain poorly understood. To address this knowledge gap, we performed transcriptomic analyses of MCL patient cohorts and identified 10 key angiogenic genes upregulated in MCL. We focused on four receptors (FGFR1, VEGFR1, VEGFR2, and PDGFRB) that have receptor tyrosine kinase activity and are localized to the plasma membranes of MCL cells. These receptors were assessed for therapeutic targeting potential in four independent preclinical models, including patient-derived xenografts, cell-derived xenografts, bone marrow-derived xenografts, and a genetically engineered murine model of MCL. Our work establishes that simultaneous targeting of multiple kinases, such as FGFR1 and VEGFR2, is a promising therapeutic strategy for patients with MCL.

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Publication Details

Journal
Biomarker Research
Published
2026-07-24
DOI
https://doi.org/10.1186/s40364-026-00975-3
Primary Topic
Angiogenesis and VEGF in Cancer
Type
article
Field-Weighted Citation Impact
0.00

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article

Identifying the angiogenic receptor expression in mantle cell lymphoma patients and murine models

Natarajan Muthusamy, Nazia Chaudhary, Virginia Amador, Neeraj Jain et al.
Biomarker Research
Angiogenesis and VEGF in Cancer
article

Identifying the angiogenic receptor expression in mantle cell lymphoma patients and murine models

Natarajan Muthusamy, Nazia Chaudhary, Virginia Amador, Neeraj Jain, Astha Soni, Jacob C. Holter, Li Zhao, Hedieh Jafari, Rosario Distefano, Blake R. Peterson, Joseph W. Tinapple, M R Berger, Alessandro La Ferlita, Uttam Kumar Nath, Lalit Sehgal, Parvathi Ranganathan, Y S Wang, Narendranath Epperla, Udita Jindal, Joseph M. Barlage, Rathan Kumar, Pui Kai Li, Jonathan W. Song, Lapo Alinari, Noura Srour, Khaliqur Rahman, Deepak Kumar, Satishkumar Singh, Samir Parekh, Robert Baiocchi, German J. Peralta-Camacho, Jihye Paik, Anuvrat Sircar, Reza Nezati
article en

Abstract

Mantle Cell Lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma, with frequent relapses and shorter responses with every subsequent treatment. MCL depends on growth factors and cytokines derived from microenvironmental cells for its growth and can alter the immune system to evade recognition and subsequent elimination. The soluble factors secreted by MCL can contribute to endothelial differentiation, lymphangiogenesis, and clonal selection under hypoxic conditions, thereby evading the DNA damage response. Targeting the tumor microenvironment and angiogenesis is an active area of research and development, as the angiogenic gene signatures in MCL remain poorly understood. To address this knowledge gap, we performed transcriptomic analyses of MCL patient cohorts and identified 10 key angiogenic genes upregulated in MCL. We focused on four receptors (FGFR1, VEGFR1, VEGFR2, and PDGFRB) that have receptor tyrosine kinase activity and are localized to the plasma membranes of MCL cells. These receptors were assessed for therapeutic targeting potential in four independent preclinical models, including patient-derived xenografts, cell-derived xenografts, bone marrow-derived xenografts, and a genetically engineered murine model of MCL. Our work establishes that simultaneous targeting of multiple kinases, such as FGFR1 and VEGFR2, is a promising therapeutic strategy for patients with MCL.

Biomarker ResearchVol. 14(1)
Fox Chase Cancer Center (US), NewYork–Presbyterian Hospital (US), Ohio Department of Education (US), Sanjay Gandhi Post Graduate Institute of Medical Sciences (IN), Central Drug Research Institute (IN), Cornell University (US), University of Utah (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), New York Hospital Queens (US), AstraZeneca (South Korea) (KR), Presbyterian Hospital (US), Advanced Centre for Treatment, Research and Education in Cancer (IN), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), All India Institute of Medical Sciences Rishikesh (IN), Weill Cornell Medicine (US), The Ohio State University (US), Icahn School of Medicine at Mount Sinai (US), Academy of Scientific and Innovative Research (IN)
National Science Foundation, American Society of Hematology, Ohio State University, Pelotonia, Department of Biotechnology, Ministry of Science and Technology, India, National Institutes of Health, Materials Research Science and Engineering Center, Harvard University, Science and Engineering Research Board, Central Drug Research Institute, National Cancer Institute, Division of Materials Research, Division of Chemical, Bioengineering, Environmental, and Transport Systems
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