ArticleClinical lymphoma, myeloma & leukemia2016
Multiparameter Analysis of Off-Target Effects of Dasatinib on Bone Homeostasis in Patients With Newly Diagnosed Chronic Myelogenous Leukemia.
Article in Clinical lymphoma, myeloma & leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Bone Marrow Edema and Tyrosine Kinase Inhibitors Treatment in Chronic Myeloid Leukemia.Diagnostics (Basel, Switzerland) · 2025Article
- Bone Effects of Anti-Cancer Treatments in 2024.Calcified tissue international · 2025Review
- Potential Off-Target Effect of Gilteritinib With Venetoclax Decreases Tumor Burden for Patients With Relapsed/Refractory Wild-TypeCase reports in hematology · 2025Article
- A phase I trial of palbociclib and bosutinib with fulvestrant in patients with metastatic hormone receptor positive and HER2 negative (HR+ HER2-) breast cancer refractory to an aromatase inhibitor and a CDK4/6 inhibitor.Contemporary clinical trials communications · 2023Article
- Peruvoside is a novel Src inhibitor that suppresses NSCLC cell growth and motility by downregulating multiple Src-EGFR-related pathways.American journal of cancer research · 2022Article
- Dasatinib in breast cancer: Src-ing for response in all the wrong kinases.Annals of translational medicine · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWe assessed patients with chronic myelogenous leukemia (CML) for serum calcium (Ca), phosphate (PO4), bone alkaline phosphatase, N-telopeptide (NTx), osteoprotegerin (OPG) levels, and trabecular bone area (TBA) in bone marrow (BM) specimens before and after treatment with dasatinib. We identified a significant increase in percentage of TBA in postdasatinib BM (P = .022). This suggests that dasatinib therapy can increase TBA without significant changes in bone and mineral metabolism. Interferences with bone homeostasis and mineral metabolism have been described in patients receiving imatinib for CML or gastrointestinal stromal tumors. Dasatinib is a potent second-generation tyrosine kinase inhibitor designed to inhibit ABL and SRC kinases while also interfering with the c-Kit, platelet-derived growth factor receptor, and STAT5 pathways. PATIENTS AND
methodsWe used a multiparameter approach to examine the off-target effects of dasatinib in 30 patients with CML treated between 2009 and 2012. We recorded serum Ca and PO4 levels, analyzed markers of bone formation (bone alkaline phosphatase/bone-specific alkaline phosphatase [BAP]) and bone resorption (NTx), measured OPG levels, and digitally analyzed changes in TBA in paired BM biopsy specimens before and after treatment. We correlated all findings with each other and with the results of conventional cytogenetic and molecular analyses.
resultsWe identified a significant increase in the percentage of TBA in postdasatinib BM biopsy specimens (P = .022) and noted a decrease in serum OPG levels in 75% of patients. Ca, PO4, BAP, and NTx levels remained steady, without significant changes. There was no correlation between biomarker levels, percentage of TBA, and/or cytogenetic or molecular response.
conclusionThese findings suggest that dasatinib therapy (within the therapeutic range) can increase trabecular bone, without causing significant changes in bone and mineral metabolism. Nonetheless, monitoring of bone health and skeletal integrity should be included into the long-term management of patients treated with dasatinib to further enhance our understanding of its safety profile and its potential role as a treatment modality for other bone diseases.
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