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NPM1

From www.haematologyetc.co.uk


Gene affected:
NPM1 - nucleophosmin1


Clinical significance
A very frequent mutation in AML, carrying a positive impact on treatment response and survival. May co-occur with FLT3-ITD mutation where the adverse impact of the FLT3 is reduced but outcome is worse than for an isolated NPM1 mutation.



Function of gene

NPM1 is a ubiquitously expressed protein that shuttles between cytoplasm and nucleus. No single precise function has emerged, and the protein probably has multiple roles, which may include involvement in centrosome duplication or ribosomal protein assembly and transport. The morphology of blast cells in NPM1 typically includes an indented nuclear appearance.


NGS panel gene coverage

Exon 12


Occurrence:


Mutation of NPM1 specifically involving exon 12 are detected in ~35% of AML cases, and in 50% of cases where there is a normal karyotype
Meta-analysis in AML has demonstrated a favourable impact for NPM1 mutations when present as a sole lesion


Associated genetic features:

  • There is a frequent association with FLT3-ITD mutation. When NPM1 mutation co-occurs with FLT3-ITD the adverse impact of FLT3 mutation is at least partly prevented, although overall results are inferior to when NPM1 mutation occurs alone.
  • The combination of NPM1 and FLT3-TKD (FLT3-tyrosine kinase domain) mutation has an outcome that appears to be equivalent to NPM1 alone.



Links


GeneWiki link:
Gene Wiki entry for NPM1
References
1. Meta-analysis of NPM1 mutation in AML