What does FLT3 ITD stand for?
The most common, which occurs in up to 34 percent of CN-AML cases, is called the FLT3 internal tandem duplication (FLT3-ITD). In this type of mutation, a short sequence of DNA is copied and inserted directly following the original sequence.
What is a FLT3 inhibitor?
FLT3 inhibitors are tyrosine kinase inhibitors and are classified into first- and second-generation inhibitors based on their kinase specificity and potency. First-generation inhibitors include midostaurin and sorafenib.
How common is FLT3 ITD?
FLT3‐ITD is found in approximately 25% of adult patients but in more than 30% of patients over 55 years of age.23, 24 In contrast, it is found in only approximately 10% of pediatric patients and in less than 5% of infant AML patients under 1 year of age.
What is the function of FLT3?
The FLT3 gene encodes a tyrosine kinase receptor that plays a key role in controlling survival, proliferation and differentiation of hematopoietic cells. Mutations in this gene are critical in causing a deregulation of the delicate balance between cell proliferation and differentiation.
What is FLT3 ITD positive AML?
Acute myeloid leukemia with a FLT3 internal tandem duplication (FLT3/ITD) mutation is an aggressive hematologic malignancy with a generally poor prognosis. It can be successfully treated into remission with intensive chemotherapy, but it routinely relapses.
What is FLT3 positive AML?
What is the FLT3 mutation? FLT3 is a gene change, or mutation, in leukemia (blood cancer) cells. It’s the most common genetic change in acute myeloid leukemia (AML), a type of leukemia that starts in the bone marrow and often moves into the blood.
How do FLT3 inhibitors work in AML?
Pim kinase inhibitors and FLT3 inhibitors show synergistic cytotoxicity in AML cells with FLT3-ITD [49,50], and Pim inhibitors restore sensitivity to FLT3 inhibitors in resistant cells [50]. The data support combining Pim kinase inhibitors, which are currently in Phase I clinical trials, with FLT3 inhibitors.
What is an IDH inhibitor?
IDH inhibitors alter the activity of IDH enzymes, resulting in reduction of α-ketoglutarate (KG) to D-2-hydroxyglutarate (2-HG), a competitive inhibitor of α-KG. From: Pharmacoepigenetics, 2019.
Can FLT3 be cured?
Overall cure rates are between 10% and 20% in AML patients with a FLT3/ITD mutation. Patients with a high FLT3/ITD allelic ratio, those with a ratio of mutant gene to wild type allele greater than 0.4, have little chance for cure.
What is a FLT3 mutation?
FLT3 is a gene change, or mutation, in leukemia (blood cancer) cells. It’s the most common genetic change in acute myeloid leukemia (AML), a type of leukemia that starts in the bone marrow and often moves into the blood. The FLT3 gene contains instructions for a protein called FLT3, which helps white blood cells grow.
Can AML FLT3 be cured?
What type of mutation is FLT3?
What is the mechanism of FLT3 inhibitors?
FLT3 inhibitors are also classified based on their mechanism of interaction with the receptor [11]. Upon activation, FLT3 undergoes a conformational change involving flipping of three residues, Asp-Phe-Gly, or DFG; active and inactive conformations are called DFG-in and DFG-out, respectively.
How are first-and second-generation FLT3 inhibitors classified?
FLT3 inhibitors are classified into first- and second-generation based on their specificity for FLT3, and into type I and type II based on their mechanism of interaction with FLT3. Table 1 FLT3 inhibitors in clinical trials in AML
How do you measure FLT3 inhibition in clinical trials?
Plasma inhibitory activity (PIA) [16] has been used as a pharmacodynamic assay for FLT3 inhibition in clinical trials. Degree of patient plasma inhibition of FLT3 phosphorylation in FLT3-ITD cell lines is measured by Western blot analysis.
What are FLT3 inhibitors for AML treatment?
FLT3 is a targetable tyrosine kinase. Several clinical trials have focused on various FLT3 inhibitors for each setting of AML treatment – frontline therapy, treatment of relapsed refractory disease, and as maintenance therapy after allogeneic HSCT. Moreover, many second-generation FLT3 inhibitor trials are ongoing, as reviewed later in the text.