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Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates. The discontinuation rate of gilteritinib for intolerance or toxicity was low (accounting for 4% of treated cases).
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http://dx.doi.org/10.1002/jha2.1045 | DOI Listing |
Background: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive form of peripheral T-cell lymphoma, accounting for 1 - 2% of non-Hodgkin lymphomas. Diagnosis is challenging, and there is no established standard first-line treatment. This case report highlights a rare progression from AITL to therapy-related acute myeloid leukemia (AML-pCT) following cytotoxic chemotherapy.
View Article and Find Full Text PDFArch Toxicol
September 2025
Mainz University Medical Center, Mainz, Germany.
Opinion Letter to Sin et al (Science Advances, 2025), Sorbate induces lysine sorbylation through noncanonical activities of class I HDACs to regulate the expression of inflammation genes.
View Article and Find Full Text PDFJ Med Chem
September 2025
Applied Pharmaceutical Science, Inc., Building 10-1, No.2, Jingyuan North Street, BDA, Beijing 100176, China.
This study reports the discovery and preclinical activity of APS03118, a novel selective RET inhibitor featuring a novel tricyclic pyrazolo[3',4':3,4]pyrazolo[1,5-]pyridine hinge-binding scaffold designed to overcome acquired resistance to first-generation selective RET inhibitors (SRIs). By enhancing hydrogen bonding with conserved hinge residues (Glu805, Ala807), APS03118 potently inhibits wild-type RET and diverse resistance mutations, including solvent-front (G810R/S/C), gatekeeper (V804M/L/E), roof (L730I/M), and hinge (Y806C/N/H) variants. In preclinical models, APS03118 induced complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient-derived xenografts (PDXs) and significantly prolonged survival in an intracranial CCDC6-RET metastasis model.
View Article and Find Full Text PDFTher Adv Hematol
September 2025
Department of Hematology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266000, China.
Myelodysplastic syndromes (MDS), particularly in older adults aged 60 years and above, present significant therapeutic challenges due to poor prognosis and limited treatment options. Higher-risk MDS (HR-MDS), defined by the Revised International Prognostic Scoring System score of ⩾3.5, is characterized by increased myeloblasts, severe cytopenia, and a median survival of <2 years.
View Article and Find Full Text PDFBioorg Chem
September 2025
Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:
RET tyrosine kinase, a key regulator of cellular signaling, is abnormally activated due to mutations or fusions in various cancers, making it an important therapeutic target. Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g.
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