Abstract
Acute myelogenous leukemia (AML) is a difficult disease to treat, and better treatments are needed. Molecular targeted therapy represents a novel therapeutic approach. The FLT3 tyrosine kinase receptor is mutated in approximately one-fourth to one-third of patients with AML. Normally, binding of FLT3 ligand to the FLT3 receptor leads to phosphorylation of tyrosine residues and activation of the receptor. This in turn leads to induction of intracellular signaling pathways essential to regulation of cell proliferation and apoptosis. Two classes of FLT3 activating mutations have been identified in AML patients: internal tandem duplications (ITDS) and point mutations in the activating loop of the kinase domain. Both mutations result in constitutive FLT3 tyrosine kinase activity and lead to transformation of hematopoietic cell lines in vivo and in vitro. FLT3 ITDs are also an independent poor prognostic factor for overall survival and disease free survival in patients with AML. Therefore, targeting FLT3 mutations represents a potential therapeutic target for AML. This review will discuss the biology and clinical significance of FLT3 and FLT3 mutations in cell growth and signaling. In addition, I will discuss some of the novel FLT3 inhibitors which are entering clinical trials for AML.
Keywords: acute myelogenous leukemia, flt mutations, targeted therapy, flt inhibitors
Current Pharmaceutical Design
Title: FLT3 and Acute Myelogenous Leukemia: Biology, Clinical Significance and Therapeutic Applications
Volume: 11 Issue: 26
Author(s): A. S. Advani
Affiliation:
Keywords: acute myelogenous leukemia, flt mutations, targeted therapy, flt inhibitors
Abstract: Acute myelogenous leukemia (AML) is a difficult disease to treat, and better treatments are needed. Molecular targeted therapy represents a novel therapeutic approach. The FLT3 tyrosine kinase receptor is mutated in approximately one-fourth to one-third of patients with AML. Normally, binding of FLT3 ligand to the FLT3 receptor leads to phosphorylation of tyrosine residues and activation of the receptor. This in turn leads to induction of intracellular signaling pathways essential to regulation of cell proliferation and apoptosis. Two classes of FLT3 activating mutations have been identified in AML patients: internal tandem duplications (ITDS) and point mutations in the activating loop of the kinase domain. Both mutations result in constitutive FLT3 tyrosine kinase activity and lead to transformation of hematopoietic cell lines in vivo and in vitro. FLT3 ITDs are also an independent poor prognostic factor for overall survival and disease free survival in patients with AML. Therefore, targeting FLT3 mutations represents a potential therapeutic target for AML. This review will discuss the biology and clinical significance of FLT3 and FLT3 mutations in cell growth and signaling. In addition, I will discuss some of the novel FLT3 inhibitors which are entering clinical trials for AML.
Export Options
About this article
Cite this article as:
Advani S. A., FLT3 and Acute Myelogenous Leukemia: Biology, Clinical Significance and Therapeutic Applications, Current Pharmaceutical Design 2005; 11 (26) . https://dx.doi.org/10.2174/138161205774370807
DOI https://dx.doi.org/10.2174/138161205774370807 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Stem Cell Niche as a Pharmaceutical Target for Prevention of Skeletal Metastases
Anti-Cancer Agents in Medicinal Chemistry Transferrin and the Transferrin Receptor: Of Magic Bullets and Other Concerns
Inflammation & Allergy - Drug Targets (Discontinued) Back to the Bench? MEK and ERK Inhibitors for the Treatment of KRAS Mutant Lung Adenocarcinoma
Current Medicinal Chemistry The Role of Matrix Metalloproteinase Inhibitors in Ischemia-Reperfusion Injury in the Liver
Current Pharmaceutical Design Radionuclide Based Imaging of Prostate Cancer
Current Topics in Medicinal Chemistry Synthesis, Characterization, Anticancer and Antibacterial Activity of Some Novel Pyrano[2,3-d]pyrimidinone Carbonitrile Derivatives
Anti-Cancer Agents in Medicinal Chemistry Omacetaxine as an Anticancer Therapeutic: What is Old is New Again
Current Pharmaceutical Design Rodent Models of Persistent Pain in Drug Discovery and Development
Current Pharmaceutical Biotechnology Preparation of Cationic Lipid-coated Ultrasound Contrast Agents and Noninvasive Gene Transfection Via Ultrasound-targeted Microbubble Destruction
Current Pharmaceutical Design Development of Nitrile-Based Peptidic Inhibitors of Cysteine Cathepsins
Current Topics in Medicinal Chemistry Genetically Modified Hepatitis B Surface Antigen: A Powerful Vaccine Technology for the Delivery of Disease-Associated Foreign Antigens
Current Drug Therapy Development of RGD-Based Radiotracers for Tumor Imaging and Therapy: Translating from Bench to Bedside
Current Molecular Medicine Evaluation of Anticancer Activities of Gallic Acid and Tartaric Acid Vectorized on Iron Oxide Nanoparticles
Drug Delivery Letters Human Genetic Variation: A Foundation for Rational Diagnosis and Individualized Treatment of Lung Cancer
Current Pharmacogenomics and Personalized Medicine Novel Substituted Quinazolines for Potent EGFR Tyrosine Kinase Inhibitors
Current Medicinal Chemistry Treatment Related Morbidity in Cervical Cancer
Current Women`s Health Reviews PEGylation: An Overview and Recent Advances Reported in the Patent Literature
Recent Patents on Chemical Engineering Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms
Current Medicinal Chemistry Molecular Imaging and Targeted Drug Delivery Using Albumin-Based Nanoparticles
Current Pharmaceutical Design Patent Selections
Recent Patents on Food, Nutrition & Agriculture