ArticleLeukemia2011
Expansion of highly differentiated CD8+ T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 98 citations in OpenAlex.
- In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy.Frontiers in immunology · 2023Trial
- Innate T-αβ lymphocytes as new immunological components of anti-tumoral "off-target" effects of the tyrosine kinase inhibitor dasatinib.Scientific reports · 2020Trial
- The longitudinal analysis of large granular lymphocytosis in patients with Philadelphia chromosome-positive leukemia treated with dasatinib.International journal of hematology · 2015Trial
- Dasatinib Exposure and Risk of CMV Reactivation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.American journal of hematology · 2026Article
- Treatment-free remission and immune profiling after frontline second-generation TKI therapy in CML.Blood advances · 2026Article
- Long-term treatment-free remission in CML after early dasatinib discontinuation due to interstitial pneumonitis.International journal of hematology · 2026Article
- Is the vIL-10 Protein from Cytomegalovirus Associated with the Potential Development of Acute Lymphoblastic Leukemia?Viruses · 2025Review
- T-cell clones of uncertain significance. When is the rogue clone dangerous?Haematologica · 2025Review
- Sustained antiviral response againstFrontiers in pharmacology · 2024Article
- Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023Article
- Proven Cytomegalovirus Colitis Associated with Dasatinib Administration in Two Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients.Pediatric gastroenterology, hepatology & nutrition · 2023Article
- Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging.Pharmaceutics · 2023Review
- Cytomegalovirus US28 regulates cellular EphA2 to maintain viral latency.Science advances · 2022Article
- BCR::ABL1 tyrosine kinase inhibitors hamper the therapeutic efficacy of blinatumomab in vitro.Journal of cancer research and clinical oncology · 2022Article
- IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia.The Journal of clinical investigation · 2022Article
- Pharmacologic control of homeostatic and antigen-driven proliferation to target HIV-1 persistence.Biochemical pharmacology · 2021Article
- Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan.JAMA network open · 2021Article
- Pivotal Role of Fyn Kinase in Parkinson's Disease and Levodopa-Induced Dyskinesia: a Novel Therapeutic Target?Molecular neurobiology · 2021Review
- Programmed cell death 1-expressing CD56-negative natural killer (NK) cell expansion is a hallmark of chronic NK cell activation during dasatinib treatment.Cancer science · 2021Article
- Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tyrosine kinase inhibitor dasatinib exerts immunosuppressive effects on T-cells and NK-cells in vitro. However, in some dasatinib-treated leukemia patients, clonal lymphocytosis with large granular lymphocyte (LGL) morphology develops, and this is associated with enhanced therapeutic responses. To elucidate the mechanistic basis for this paradoxical observation, we conducted detailed phenotypic and functional analyses of T-cell and NK-cell populations from 25 dasatinib-treated leukemia patients. All tested patients with LGL expansions (15/16) were cytomegalovirus (CMV) immunoglobulin (IgG) seropositive with high frequencies of CMV-specific CD8(+) T-cells; 5/16 LGL patients also experienced symptomatic CMV reactivation during dasatinib therapy. Expanded T-cell and NK-cell populations exhibited late differentiated (CD27(-)CD57(+)) phenotypes; this was associated with a predisposition to apoptosis within the T-cell compartment and impaired NK-cell cytotoxicity. Only 3/9 non-LGL patients were CMV IgG seropositive. Dasatinib inhibited in vitro lymphocyte functions, similarly in LGL patients and controls. Notably, distinct CD8(high) and CD8(low) T-cell subsets were observed in LGL patients; this phenotypic dichotomy was also apparent in CMV-specific CD8(+) T-cell populations, and exhibited features consistent with antigen-driven activation. In addition, plasma levels of IP-10, IL-6, monokine induced by interferon-γ and interleukin-2R were significantly increased in LGL patients. These data provide evidence that dasatinib-associated LGL expansion is linked to CMV reactivation and suggest a potential mechanism for this phenomenon.
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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 OpenQuestion graph.