FLT3wildtype

FLT3 wild-type refers to the absence of activating mutations in the FLT3 gene, a receptor tyrosine kinase involved in hematopoietic cell proliferation. In clinical practice, FLT3 wild-type status is most commonly discussed in acute myeloid leukemia (AML), where it denotes that no FLT3 internal tandem duplications (ITD) or tyrosine kinase domain (TKD) mutations have been detected. FLT3 mutations occur in about 30% of AML cases, with ITD being more common than TKD mutations; consequently, a substantial fraction of AML patients are FLT3 wild-type.

Prognostically, FLT3 wild-type AML does not carry the adverse prognosis usually associated with FLT3-ITD, though outcomes depend on other factors such as cytogenetic risk category and patient age. FLT3 wild-type status therefore represents a broad group with heterogeneous prognoses, ranging from favorable to intermediate, depending on additional molecular and clinical features.

Diagnostic assessment for FLT3 status involves molecular testing, typically using polymerase chain reaction (PCR) and fragment analysis to detect ITD, and sequencing-based methods to identify TKD mutations. Next-generation sequencing (NGS) panels may also be used to confirm FLT3 status and to identify co-occurring mutations that influence prognosis and treatment decisions.

Therapeutically, FLT3 inhibitors (for example, midostaurin or gilteritinib) are approved for AML with FLT3 mutations and are not generally indicated for FLT3 wild-type disease outside of clinical trials. Standard AML treatment regimens, including chemotherapy and consideration of allogeneic stem cell transplantation for eligible patients, remain the mainstay for FLT3 wild-type AML, while research continues on therapies with broader activity or combination strategies.

See also: FLT3, acute myeloid leukemia, ITD, TKD.