FLT3

Mutations of FLT3, especially of the internal tandem duplication, or among most common in acute myelogenous leukemia.

FMS-like tyrosine kinase 3 (FLT3), a cytokine receptor tyrosine kinase that is expressed in early for hematopoetic stem and progenitor cells, regulates their proliferation and differentiation.

Activation of the mutated FLT3 receptor and activation of multiple downstream signaling pathways promote this regulated growth and proliferation.

A trans-membrane receptor tyrosine kinase that is mutated in about 30% of AML cases.

A driver of proliferation, and therefore its presents suggest a significant proliferative disease.

In cytogenetically normal AML patients the presence of FLT3 mutations is associated with a high percentage of peripheral blood and bone marrow blasts.

The FLT3 mutation is the most common mutation in AML. 


FLT3 mutations occur in approximately 25% of adults with AML. 

FLT3  AML is associated with very high white cans, large burden of leukemia suggesting a bad prognostic sign.

The FLT3  mutation most commonly occurs with the nucleophomin 1 mutation.

The prognosis of FLT3 internal tandem duplication in AML is related to the allelic ratio, length, insertion, site, and co-occurring mutations.

Patients with a high FLT three-internal tandem duplication allelic ratio is greater than .5 have a worse prognosis than those with wild type FLT3  acute myelogenous leukemia, and are rarely cured by chemotherapy alone.

There are two types of mutations in the FLT3 gene that render it permanently activated.

FLT3-internal tandem duplications (ITD)correlate with increased risk of relapse and poorer progression-free and overall survival in AML.

FLT3-internal tandem duplications occurs in 20-30% of patients with AML.

In patients with AML, the presence of FLT3-internal tandem duplications adversely affect survival, both at diagnosis and failure of initial therapy.

FLT3 internal tandem duplication mutation is the most common mutation, and it is an inserted coding sequence, located in the specific area of the receptor that normally is responsible for keeping the gene off in a controlled fashion: altering the natural suppression of the receptor and the gene stays active.

The second FLT3 mutation is less common and occurs in approximately 7% of patients with AML: FLT3-tyrosine kinase domain.

Inhibitors of FLT3 are midostaurin and gilteritinib.

In AML FLT3-TKD and NPM1 mutations, when they occur  together indicate a better prognosis.

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