FLT3 overexpression is a recurrent event in various acute leukaemia subtypes. This transcriptional deregulation is important to define the prognostic risk for many patients. Of note, the molecular mechanisms leading to this gene upregulation are unknown for a substantial number of cases. In this Mini-Review, we highlight the role of FLT3 overexpression in acute leukaemia and discuss emerging mechanisms accounting for this upregulation. The benefits of using targeted therapy are also addressed in the overexpression context, posing other therapeutic possibilities based on state-of-the-art knowledge that could be considered for future research.
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http://dx.doi.org/10.1016/j.bbcan.2019.06.001 | DOI Listing |
Int J Mol Sci
January 2025
Centro de Investigación Biomédica en Red de Cáncer, CIBERONC CB16/12/00284, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Recent studies have demonstrated the association between constitutional ring chromosome 21 (r(21)c) and the development of B-cell acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21). iAMP21 acts as a driver which is often accompanied by secondary alterations that influence disease progression. Here, we report an atypical case of iAMP21 B-ALL with a unique molecular profile in the context of r(21)c.
View Article and Find Full Text PDFCancer Lett
January 2025
Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China. Electronic address:
Front Pediatr
December 2024
Laboratory of Translational Research, Children's Hospital of Brasília, Brasília, Brazil.
Introduction: There is consistent evidence that may be a driver gene in B-ALL and that selected cases may benefit from the use of FLT3 inhibitors. Our study was conducted to evaluate the frequency and types of FLT3 mutations in pediatric patients with B-ALL, the relative expression of this gene, and their influence on clinical evolution.
Methods: We evaluated 156 children with B-ALL treated between July 2018 and September 2023.
J Cell Mol Med
December 2024
Menarini Group, Preclinical and Translational Sciences, Pomezia, Rome, Italy.
MEN1703 is a first-in-class, oral, Type I dual PIM/FMS-like tyrosine kinase 3 inhibitor (FLT3i) investigated in a Phase I/II DIAMOND-01 trial in patients with acute myeloid leukaemia (AML). Gilteritinib is a highly potent and selective oral FLT3i approved for the treatment of relapsed/refractory AML with FLT3 mutations. Although gilteritinib showed strong single-agent activity in FLT3-mutated AML, the development of gilteritinib resistance limits response durability, indicating the importance of novel combination strategies to improve disease outcome.
View Article and Find Full Text PDFDrug Dev Res
December 2024
Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, Jiangsu, China.
The abnormal overexpression of FLT3 kinase is intimately associated with pathogenesis of acute myeloid leukemia (AML), positioning FLT3 inhibitors as pivotal therapeutic agents. Despite the availability of three FDA-approved FLT3 inhibitors, their clinical utility is hampered by resistance stemming from tyrosine kinase domain (TKD) mutations. Through an integrative analysis of case studies, we identified a potential advantage of type I FLT3 inhibitors in overcoming TKD mutation-induced resistance.
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