NPM1 gene sequence analysis
Definition
NPM1 mutations occur in approximately 25-35% of de novo AML cases and 45-60% of normal-karyotype AML, making it the most common single-gene mutation in AML. Most of these mutations (75-80% of adult NPM1-mutant AML) are a frameshift caused by a 4-base insertion in exon 12 (most commonly 'type A'), which disrupts the nuclear localization signal of the nucleophosmin protein, leading to its abnormal cytoplasmic accumulation (NPMc+). In the absence of a concurrent FLT3-ITD mutation, an isolated NPM1 mutation falls into the favorable (good prognosis) group in the 2022 ELN risk classification; when present together with FLT3-ITD, this advantage is lost.
Gene/region examined
NPM1 Exon 12
Method
DNA analysis
Accepted sample types
Blood (EDTA), Bone marrow (EDTA)
Description
Acute Myeloid Leukemia (AML) prognosis determination.
Inheritance
In AML, NPM1 exon 12 mutations are almost invariably somatic (acquired, arising in the leukemic clone); no hereditary AML predisposition syndrome associated with germline NPM1 mutation has been defined.