ArticleBlood2005
Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation.
Article in Blood, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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The trial behind it
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
87 citing papers in PubMed, 240 citations in OpenAlex.
- Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial.Leukemia · 2018Trial
- Midostaurin does not prolong cardiac repolarization defined in a thorough electrocardiogram trial in healthy volunteers.Cancer chemotherapy and pharmacology · 2012Trial
- Experience with everolimus (RAD001), an oral mammalian target of rapamycin inhibitor, in patients with systemic mastocytosis.Leukemia & lymphoma · 2010Trial
- A pilot study of nonmyeloablative allogeneic hematopoietic stem cell transplant for advanced systemic mastocytosis.Bone marrow transplantation · 2006Trial
- Mastocytosis.Nature reviews. Disease primers · 2025Review
- Beyond the Usual Suspects: Unraveling Spleen Mastocytosis in Hypersplenism Differential Diagnosis.Cureus · 2024Article
- Recent Advances in the Therapeutic Management of Advanced Systemic Mastocytosis.Diagnostics (Basel, Switzerland) · 2023Review
- Recent advances in diagnosis and therapy in systemic mastocytosis.Blood research · 2023Review
- Available and emerging therapies for bona fide advanced systemic mastocytosis and primary eosinophilic neoplasms.Hematology. American Society of Hematology. Education Program · 2022Review
- Clinical challenge for gastroenterologists-Gastrointestinal manifestations of systemic mastocytosis: A comprehensive review.World journal of gastroenterology · 2022Review
- Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia.International journal of molecular sciences · 2022Review
- Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials.Pharmaceutics · 2021Review
- Precision Medicine in Systemic Mastocytosis.Medicina (Kaunas, Lithuania) · 2021Review
- Inhibition of KIT Tyrosine Kinase Activity: Two Decades After the First Approval.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
- [Spectrum of gene mutations and clinical features in adult acute myeloid leukemia with normal karyotype].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- Turning liabilities into opportunities: Off-target based drug repurposing in cancer.Seminars in cancer biology · 2021Review
- Systemic Mastocytosis: Molecular Landscape and Implications for Treatment.Mediterranean journal of hematology and infectious diseases · 2021Review
- Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts.Theranostics · 2020Review
- ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KIT.Cancer research · 2019Article
- Multidisciplinary Challenges in Mastocytosis and How to Address with Personalized Medicine Approaches.International journal of molecular sciences · 2019Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Limited treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). We evaluated whether PKC412, a small-molecule inhibitor of KIT with a different chemical structure from imatinib, may have therapeutic use in advanced SM with the D816V KIT mutation. We treated a patient with MCL (with an associated myelodysplastic syndrome (MDS)/myeloproliferative disorder [MPD]) based on in vitro studies demonstrating that PKC412 could inhibit D816V KIT-transformed Ba/F3 cell growth with a 50% inhibitory concentration (IC50) of 30 nM to 40 nM. The patient exhibited a partial response with significant resolution of liver function abnormalities. In addition, PKC412 treatment resulted in a significant decline in the percentage of peripheral blood mast cells and serum histamine level and was associated with a decrease in KIT phosphorylation and D816V KIT mutation frequency. The patient died after 3 months of therapy due to progression of her MDS/MPD to acute myeloid leukemia (AML). This case indicates that KIT tyrosine kinase inhibition is a feasible approach in SM, but single-agent clinical efficacy may be limited by clonal evolution in the advanced leukemic phase of this disease.
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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.