Rapid AML Panel

Mutations in the FLT3 gene are common mutations in acute myeloid leukemia (AML). This assay detects internal tandem duplication (ITD) mutations and mutations in the tyrosine kinase domain (TKD) of FLT3. Presence of these mutations in AML provide prognostic information and can aid in the determination of therapeutic regimen.

FLT3 is a receptor tyrosine kinase (RTK) that dimerizes on binding its ligand, the cytokine FLT3 ligand (FL), which then undergoes autophosphorylation, and transduces signals downstream (STAT, AKT, ERK) that promote proliferation and survival. Activating mutations of FLT3 are common mutations found in AML. A particular form of FLT3 is mutated by duplicating coding sequence derived from the juxtamenbrane domain inserted in tandem (internal tandem duplication (ITD). These FLT3-ITD mutations result in the constitutive activation of the tyrosine kinase function. Patients with FLT3-ITD mutations have increased relapse rates and reduced overall survival. Point mutations in the activation loop of the kinase domain, most commonly at the residue Asp 835 (D835), also known as tyrosine kinase domain (TKD) mutations, also result in the constitutive activation of the FLT3 kinase. Signaling from FLT3-TKD mutations does not appear as abnormal, and the prognostic impact appears to be less severe when compared with ITD mutations (FLT3-ITD mutations are found in approximately 23% of AML cases, whereas TKD mutations are found in 7%).

NPM1 (nucleophosmin) mutation is one of the most common recurring genetic lesions in acute myeloid leukemia (AML). This AML type frequently has myelomonocytic or monocytic features and typically presents de novo in older adults with a normal karyotype. Prevalence increases with age, occurring in 2% to 8% of childhood AML and 27% to 35% of adult AML. The most common mutations a 4 bp duplication at c.860_863 (exon 11) or insertion at c.863_864 (exon 11), accounts for 90% to 95% or NPM1 mutations. NPM1 mutations in absence of FLT3-ITD identify a prognostically favorable subgroup.

IDH 1/2 Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are the most frequently mutated metabolic genes in human cancer. They encode cytosolic and mitochondrial enzymes that catalyze the conversion of isocitrate to a-ketoglutarate (aKG), a key component in metabolic and cellular pathways including the Krebs cycle. IDH1 and IDH2 mutations are found in multiple types of human cancer including, but not limited to, acute myeloid leukemia and gliomas. Identification of IDH mutations can aid in their diagnosis, provide prognostic information and suggest treatment with IDH inhibitors. This assay will detect mutations affecting amino acids 100 and 132 of IDH1 and amino acids 140 and 172 of IDH2.