Publication details
Úloha FLT3 mutací v patogenezi akutní myeloidní leukemie
| Title in English | The role of FLT3 mutations in the pathogenesis of acute myeloid leukemia |
|---|---|
| Authors | |
| Year of publication | 2009 |
| Type | Article in Periodical |
| Magazine / Source | Transfuze a hematologie dnes |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | FLT3 receptor tyrosine kinase; cyogenetically normal AML; internal tandem duplication; prognostic marker |
| Description | FLT3 (FMS-like tyrosine kinase 3) is a tyrosine kinase receptor expressed by early hematopoietic progenitor cells and is essential fot its normal development and proliferation. Activating mutations of this kinase are found in approximately 40% of all AML cases and are therefore on of the most common genetic alterations observed in AML. Mutations in FLT3 gene lead to constitutive phosphorylation of the receptor and consecutive activation of downstream signalling pathways resulting in uncontrolled cell proliferation. FLT3 mutational status, especially internal tandem duplications in exons 14 and 15, appears to be a significant prognostic indicator associated with a distinctly worse clinical outcome in AML patients with normal cytogenetics in terms of shorter complete remission duration (CRD) and disease free survival (DFS). Prognostic imapct of point mutations in tyrosine kinase domain is less clear and is still under debate. High frequency of FLT3 mutations and its prognostic relevance in both adult and pediatric AML makes it an appropriate target for therapy. There are several FLT3 tyrosine kinase inhibitors tested in ongoing preclinical and clinical trials. |