Acute Myeloid Leukemia Mutatio

The Human Acute Myeloid Leukemia (AML) qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid, accurate and comprehensive profiling of recurrent frequent somatic mutations found in in human AML samples. Patients with AML, the most frequent hematological malignancy in adults, have highly variable prognoses and a high mortality rate. Mutations in a number of genes have been implicated in the pathogenesis of AML, including ASXL1, DNMT3A, FLT3, IDH1, IDH2, KIT, NPM1, NRAS, RUNX1, TET2 and WT1. Detection of somatic molecular abnormalities that may cause and maintain AML is crucial for patient sample stratification in translational research studies. These mutations also warrant extensive investigation to enhance the understanding of carcinogenesis and identify potential drug targets. With its comprehensive content coverage, this array is designed for studying mutations in the context of AML and has the potential for discovering and verifying AML biomarkers. The 83 real-time PCR DNA sequence assays included on the array detect the most frequent, functionally verified, and biologically significant mutations in AML. These mutations were chosen from curated, comprehensive somatic mutation databases and peer-reviewed scientific literature. The simplicity of the product format and operating procedure allows routine somatic mutation profiling in any research laboratory with access to real-time PCR instruments.

ASXL1: 5 Assays
Most frequently observed mutations in this gene are C-terminal truncations that lose the interaction domain with RARA, the poly-serine region, and the atypical PHD-type domain. Other truncations also lose part of the NCOA1 interaction domain and a glycine-rich region.

DNMT3A: 2 Assays
Mutations are frequently observed in the domain conserved among S-adenosylmethionine-dependent methyltransferases superfamily members.

FLT3: 5 Assays
The most frequently identified FLT3 mutations include point mutations, insertion and deletion mutations in the juxtamembrane and activation domains of the protein.

IDH1: 5 Assays
Most of these mutations abolish magnesium binding and alters the enzyme's activity to convert alpha-ketoglutarate into R(-)-2-hydroxyglutarate instead of isocitrate into alpha-ketoglutarate.

IDH2: 7 Assays
These mutations all lie in the substrate binding domain, and one (p.R140Q) is associated with D-2-hydroxyglutaric aciduria.

KIT: 24 Assays
The most frequently identified KIT gain-of-function mutations include the D816V point mutation, the exon 11 (juxtamembrane domain) deletion and point mutations, an exon 9 insertion mutation, and exon 13 point mutations.

NPM1: 5 Assays
NPM1 encodes a phosphoprotein that shuttles between the nucleus and the cytoplasm and is thought to be involved in regulation of the ARF/p53 pathway. A number of gene fusion events with NPM1 have been characterized, in particular the anaplastic lymphoma kinase gene on chromosome 2. Mutations in this gene are associated with acute myeloid leukemia.

NRAS: 17 Assays
The mutation assays include the most important NRAS mutations at codons 12, 13, and 61.

RUNX1: 7 Assays
RUNX is the alpha subunit of the core binding factor that is thought to be involved in normal hematopoiesis. Chromosomal translocations involving this gene have been associated with several types of leukemia.

TET2: 2 Assays
The most common variants of this gene are C-terminal truncations missing its two glutamine-rich regions, all of its metal binding site residues, and a phosphoserine and a phosphotyrosine site.

WT1: 4 Assays
The WT1 transcription factor plays an essential role in normal urogenital system development. A small subset of patients with Wilm's tumors contains mutations in this gene.