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Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML).  NPM1  mutations are always heterozygous. In addition,  NPM1  has a number of different splice variants with the major variant encoded by exons 1–9 and 11–12 ( NPM1.1 ). Further variants include  NPM1.2  which lacks exons 8 and 10 and  NPM1.3  which comprises exons 1–10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without  NPM1  mutations and also assessed the level of expression from the wild-type and mutant alleles in variants  NPM1.1  and  NPM1.2.  The results show that  NPM1.1  is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance.

Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia