NPM1

• About this biomarker
• Introduction to our products
• Why choose our products
• Main products for NPM1
• Associated products
• Related publications

The group of “cytogenetically normal” patients constitutes approx. 50% of all adult AML. This category of patients is however extremely heterogeneous with regard to their pre-treatment clinical features and optimal treatment strategies. Molecular subtyping of AML with normal karyotype contributes to a better stratification and management of these patients [Löwenberg B. ASH Educ Program Hematology 2008].

In 2005, Falini et al. [Falini B et al. Review – Blood. 2007] identified mutations in exon 12 of the NPM1 gene. NPM1 mutations are AML-specific and observed in 50 to 60 % of AML with normal karyotype, i.e. 1/3 of all adult AML. It is closely associated with de novo AML. More than fifty different NPM1 mutations have been described on the NPM1 gene.

NPM1 mutations disrupt at least one Tryptophan residue at the C terminus, and create a new nuclear export signal and an elongated NPM1 protein (nucleophosmin) that localizes aberrantly in the cytoplasm (NPMc+ AML). Except for 2 cases (involving the splicing donor site of exon 9 and exon 11), mutations are restricted to exon 12. The most prevalent types of mutations (4bp insertions) occur in a hotspot located at positions 956 to 959 (NM_002520) [Rau R et al. Hematol. Oncolo. 2009] and are identified as Mutation A (~75-80%), Mutation B (~10%) and Mutation D (~5%); all other mutations are very rare. NPM1 is frequently associated with a mutation of FLT3 in the same AML.

Detection of the presence of an NPM1 mutation is now part of clinical diagnostic algorithms and an important step in the management of AML with normal karyotype:

• AML with mutated NPM1 represents a provisional AML entity in the 2008 WHO classification
• The presence of an NPM1 mutation confers a favorable prognosis in the absence of FLT3 mutation, and an intermediate prognosis if combined with an FLT3 mutation [Döhner H et al. Blood. 2010]
• Because of stability of the NPM1 mutation, its quantification may represent a tool for Minimal Residual Disease (MRD) and treatment response monitoring. Recent publications support this strategy which requires further documentation [Krönke J et al. JCO. 2011].

IPSOGEN proposes a complete solution for NPM1 mutation testing, from mutational status identification to mutation load quantification:

• NPM1 MutaScreen™ kit uses Real-Time PCR Clamp technology to define NPM1 mutational status (mutated or wild type) and identify NPM1 mutation type (A, B or D).
• NPM1 MutaQuant® kits use Real-Time Quantitative PCR technology to quantify specific NPM1 mutation (A, B or D) expression relative to ABL control gene expression.

Why choose NPM1 MutaScreen™ kit?

• Detection, on genomic DNA, of:
  • Total NPM1 (wild-type + mutated)
  • Mutated NPM1
  • NPM1 Mut A, Mut B and Mut D separately
• Two results at the same time:
  • NPM1 mutational status (mutated or wild type)
  • Identification of NPM1 mutation type (A, B or D)
• Product manufactured under ISO 13485 certification ensuring optimal quality control and full traceability
• Positive and negative controls