Stains & CD markers

Last staff update: 6 June 2023 (update in progress)

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PubMed Search: NPM1

Jan Bosch-Schips, M.D.
Christian M. Schürch, M.D., Ph.D.
Page views in 2022: 65
Page views in 2023 to date: 52
Cite this page: Bosch-Schips J, Schürch CM. NPM1. website. Accessed June 10th, 2023.
Definition / general
  • Nucleophosmin (NPM1) is located on chromosome 5q35.1 and encodes a multifunctional protein predominantly located in the nucleolus but with shuttling capability to the nucleus and cytoplasm
  • Mutations in NPM1 are associated with myeloid neoplasms, namely acute myeloid leukemia (AML)
Essential features
  • Multifunctional protein participating in multiple cellular processes
  • NPM1 mutated AML is recognized as a genetically defined entity in the 2017 World Health Organization (WHO) classification of hematopoietic neoplasms
  • Aberrant cytoplasmic staining by immunohistochemistry (IHC) is a surrogate that strongly supports underlying NPM1 mutation
  • NPM1 is involved in the t(2;5)(p23;q35) NPM1::ALK translocation in anaplastic large cell lymphoma (ALCL)
  • NPM1, nucleophosmin 1, nucleophosmin, nucleolar phosphoprotein B23, numatrin
  • NPM1 is a multifunctional protein taking part in (Biochem Res Int 2011;2011:195209, Int J Mol Sci 2021;22:10040)
    • Ribosome biogenesis
    • Histone chaperoning
    • Centrosome duplication
    • DNA repair
    • Chromatin remodeling
    • RNA helix destabilizing activity
    • Regulation of alternative reading frame (ARF) p53 tumor suppressor pathway
    • Inhibition of caspase activated DNase
    • Prevents apoptosis when located in the nucleolus
  • NPM1 is predominantly located in the nucleolus but with shuttling capability to the nucleus and cytoplasm (Blood 2020;136:1707, Haematologica 2007;92:519)
  • NPM1 mutation is likely related to errors during DNA replication that are stimulated by improper activity of terminal deoxynucleotidyl transferase (Leuk Res 2020;99:106462)
  • Exon 12 alterations can cause a change in the position of nucleophosmin within the cell (Leukemia 2017;31:798)
    • More recently, novel non-exon 12 NPM1 mutations, such as exon 5 mutations, also reinforce nucleophosmin cytoplasmic relocation as critical for leukemogenesis (Blood 2021;138:2696)
  • NPM1 mutation stimulates elevated HOXA and HOXB gene expression (Cancer Cell 2018;34:499)
  • FLT3, DNMT3A and IDH1 / 2 genes are frequently mutated in conjunction with NPM1 (Am J Hematol 2019;94:913, J Hematol Oncol 2008;1:10)
  • NPM1 mutation in a context of clonal hematopoiesis of undetermined significance harboring a DNMT3A mutation can progress to a myeloproliferative neoplasm (Leukemia 2019;33:1635)
  • NPM1 can fuse with ALK in the t(2;5)(p23;q35) chromosome translocation in ALCL (Haematologica 2007;92:519)
Clinical features
Uses by pathologists
  • Aberrant cytoplasmic staining by IHC can be used as a surrogate supporting NPM1 mutation
  • IHC is typically performed in AML with monocytic and myelomonocytic phenotype, as well as in myeloid sarcoma
  • NPM1 can be identified through FISH probes when detecting NPM1::ALK fusion / translocation in anaplastic large cell lymphoma (Cancers (Basel) 2021;13:144)
Prognostic factors
  • In AML, mutated NPM1 in the context of normal karyotype and absence of FLT3 internal tandem duplication mutation has a more favorable prognosis (Dis Markers 2013;35:581)
  • Multilineage dysplasia has no prognostic impact in NPM1 mutated AML (Blood 2010;115:3776)
  • Prognostic biomarker in gastric cancer, in which NPM1 high expression groups are associated with a better overall survival rate (Neoplasma 2022;69:965)
Microscopic (histologic) images

Contributed by Leonie Frauenfeld, M.D.
NPM1 wild type AML

NPM1 wild type AML

NPM1 mutated AML NPM1 mutated AML

NPM1 mutated AML

Positive staining - normal
  • Normal tissues (ubiquitous nuclear expression)
Positive staining - disease
Negative staining
  • NPM1 expression is heterogeneous in gastric tumors (BMC Gastroenterol 2014;14:9)
    • Downregulation may have a role in gastric carcinogenesis
Molecular / cytogenetics description
Sample pathology report
  • Bone marrow, trephine biopsy:
    • NPM1 mutated acute myeloid leukemia (see comment)
    • Comment: Hypercellular bone marrow for age involved by acute myeloid leukemia. Increase of immature cells with myelomonocytic differentiation is seen. NPM1 immunohistochemistry shows aberrant nuclear and cytoplasmic positivity, supporting the notion of an underlying mutation ultimately confirmed by molecular analysis.
Board review style question #1

Which of the following staining patterns in myeloid cells strongly supports underlying NPM1 mutation?

  1. Golgi staining
  2. Loss of expression
  3. Membrane staining
  4. Nuclear and cytoplasmic staining
  5. Strictly nuclear staining
Board review style answer #1
D. Nuclear and cytoplasmic staining. NPM1 is predominantly located in the nucleolus but has shuttling capability to the nucleus and cytoplasm. Nuclear and aberrant cytoplasmic NPM1 expression in neoplastic cells supports an underlying NPM1 mutation. Answers A and C are incorrect because the mutation leads to enhanced cytoplasmic staining, not Golgi or membrane staining. Answer B is incorrect because NPM1 is still detectable even if mutated. Answer E is incorrect because strictly nuclear staining is considered normal.

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Reference: NPM1
Board review style question #2
Which of the following morphologies is NPM1 mutated AML most frequently associated with?

  1. Erythroblastic
  2. Megakaryoblastic
  3. Monocytic and myelomonocytic
  4. Myeloid
  5. Undifferentiated
Board review style answer #2
C. Monocytic and myelomonocytic. NPM1 mutated AML is strongly associated with myelomonocytic and monocytic morphology (Blood 2007;109:874).

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Reference: NPM1
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