FLT3 mutations
Mutations in the fms-like tyrosine kinase-3 gene (FLT3) gene are common in AML and are present in approximately 30% of diagnoses. The most common abnormality in FLT3 (23-34%) are internal tandem duplication (FLT3-ITD). FLT3-ITD encodes an abnormal protein that induces dimerization and constitutive activation of STAT5, JAK2 and MAPK pathways leading to increased proliferation and cell survival. Internal tandem duplication of FLT3 (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in AML patients with intermediate-risk karyotype at diagnosis.
Patients affected by AML caused by mutations in the FLT3 gene are characterized by normal cytogenetics, leukocytosis and monocytic differentiation. Furthermore, FLT3 mutations are associated with poor prognosis and this form of leukemia has a lower survival rate and a higher rate of relapse.
