NPM1 Mutation Analysis – Small Insertion Analysis in Acute Myeloid Leukemia


Nucleophosmin (NPM) is reported as the most frequent mutation in AML, especially in presence of a normal karyotype (~30-50%). NPM is a nuclear-cytoplasm shuttling protein, known to be involved in gene rearrangements in leukemia and lymphoma. NPM in AML is mutated by inserts and deletions within the exon 12 region, encoding a nucleic acid binding domain and the C-terminal export signal of the protein. Normally, NPM is located in the nucleolus and the nuclear membrane. Mutated NPM protein shows an aberrant cytoplasmic localization and has insertion/duplication between tryptophan residues codon 288 and 290. A normal karyotype and a mutated NPM generally predict a good response to induction therapy.

Clinical Utility

AML with mutated NPM1 is a provision diagnostic category in the 2008 WHO classification for AML.


Loci Tested: NPM1 Insertions between codons 288 and 290

The exon 12 region of the NPM1 gene is amplified in a single PCR reaction using a labeled primer. The amplification yields a characteristic size in normal or wild-type genotype. Insertions which may occur in AML are detected by fragment analysis to detect an altered size in the fragment.


Twice per week

Turnaround time

Within 7-10 business days of receipt



Specimen Requirements

  1. Peripheral Blood: 3-5 ml, collected in EDTA (purple top) tube, store at room temperature 24 hours
  2. Bone Marrow: 0.5-1 ml, collected in EDTA (purple top)tube, store at room temperature, 24 hours
  3. Unacceptable Specimens: Frozen blood or bone marrow specimens are unacceptable as are tissue samples that have undergone a freeze/thaw cycle(s).

Shipment Must Include

Requisition form
Patient pathology report


  1. Boissel, N. et al, (2005), Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype, Blood, vol 106(10), pp.3618-3620.