ArticleJournal of cellular and molecular medicine2023
PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target.
Article in Journal of cellular and molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 6 citations in OpenAlex.
- Focal adhesion kinase FAK interplays with ROR1 in the aggressiveness of chronic lymphocytic leukemia.BMC medicine · 2026Article
- B cell mechanobiology in health and disease: emerging techniques and insights into therapeutic responses.FEBS letters · 2025Review
- Focal adhesion kinase-mediated interaction between tumor and immune cells in the tumor microenvironment: implications for cancer-associated therapies and tumor progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Focal adhesion kinase signaling - tumor vulnerabilities and clinical opportunities.Journal of cell science · 2024Review
- Focal adhesion kinase as a new player in the biology of onco-hematological diseases: the starting evidence.Frontiers in oncology · 2024Review
- PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target.Journal of cellular and molecular medicine · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose-response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.