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Intrachromosomal amplification of chromosome 21 (iAMP21) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in children is a high-risk subtype for which targeted drugs are lacking. In this study, we determined the frequency of secondary lesions in 28 iAMP21 BCP-ALL patient samples and investigated cellular sensitivity for candidate-targeted drugs. iAMP21 was enriched in aberrations (10.
View Article and Find Full Text PDFPrognostic, biological, and structural implications of FLT3-JMD point mutations in acute myeloid leukemia: an analysis of Alliance studies.
Leukemia
January 2025
The Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients.
View Article and Find Full Text PDFAdvances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies.
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Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
FLT3 mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Significant advancements have been made in developing FLT3 inhibitors (FLT3Is), such as quizartinib, which have improved treatment outcomes in both newly diagnosed and relapsed/refractory AML. Resistance to FLT3Is remains a major clinical challenge, driven by diverse mechanisms including FLT3 point mutations, cellular escape pathways, and the influence of the bone marrow microenvironment.
View Article and Find Full Text PDFUnveiling the substantial role of rutin in the management of drug-induced nephropathy using network pharmacology and molecular docking.
Int Immunopharmacol
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M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University) Mullana, Ambala, Haryana, India. Electronic address:
Introduction: Flavonoids including quercetin, kaempferol, myricetin, rutin etc. have always been a part of traditional Chinese medicine for the treatment of several ailments. Rutin (RT), also known as rutoside, sophorin is one of the flavanol glycoside having structure resemblance with quercetin.
View Article and Find Full Text PDFTargeting FMS-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia: Novel molecular approaches and therapeutic challenges.
Biomed Pharmacother
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Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove 500 05, Czech Republic. Electronic address:
Acute myeloid leukemia (AML), a heterogeneous hematologic malignancy, has generally a poor prognosis despite the recent advancements in diagnostics and treatment. Genetic instability, particularly mutations in the FMS-like tyrosine kinase 3 (FLT3) gene, is associated with severe outcomes. Approximately 30 % of AML patients harbor FLT3 mutations, which have been linked to higher relapse and reduced survival rates.
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