FLT3mutated

FLT3mutated refers to the presence of activating mutations in the FLT3 gene, most commonly internal tandem duplications (ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain (TKD), such as D835. FLT3 encodes a receptor tyrosine kinase expressed on hematopoietic progenitor cells. Mutations lead to constitutive activation of signaling pathways that promote proliferation and survival of myeloid blasts.

In acute myeloid leukemia (AML), FLT3 mutations occur in about 30% of adults; FLT3-ITD roughly 20–25% and TKD about 5–10%. The presence of FLT3-ITD is associated with higher relapse risk and poorer overall survival, although prognosis is influenced by factors such as the ITD allelic ratio and co-occurring mutations (for example NPM1). FLT3-TKD mutations carry variable prognostic significance.

FLT3 mutation status is determined by molecular testing on diagnostic samples. ITD is typically detected by PCR-based fragment analysis with measurement of the ITD length and allelic ratio; TKD mutations are detected by sequencing methods, including Sanger or targeted next-generation sequencing. Testing of relapse samples can aid treatment decisions.

In newly diagnosed FLT3-mutated AML, the addition of an FLT3 inhibitor to induction chemotherapy improves outcomes (for example, midostaurin in the RATIFY trial). In relapsed or refractory disease, gilteritinib has shown superior survival compared with chemotherapy in the ADMIRAL trial. Other inhibitors such as quizartinib and crenolanib are under investigation or approved in certain contexts. Allogeneic stem cell transplantation is often considered in first remission when feasible due to relapse risk. The term FLT3mutated is used to denote FLT3-ITD or TKD-mutant AML and informs prognosis and treatment planning.