Cytoplasmic nucleophosmin in acute myeloid leukaemia with a normal karyotype
This study discovered that about a third of acute myeloid leukaemias, and most with normal chromosomes, carry a mutation in the NPM1 gene that displaces its protein into the cytoplasm, defining a distinct and relatively favourable form of the disease.
Overview
Immunohistochemical and sequencing study of 591 AML cases showing cytoplasmic nucleophosmin in 35 percent, almost always caused by mutations in exon 12 of NPM1, concentrated in normal-karyotype AML (about 50 to 60 percent), associated with monocytic features, CD34 negativity and a good response to induction chemotherapy in the absence of FLT3-ITD.
- Cytoplasmic NPM1 in 35.2 percent of primary AML and in the majority of normal-karyotype cases.
- Associated with higher complete remission rates and mutual exclusivity with recurrent translocations.
NPM1-mutated AML is now its own WHO category. The mutation is a stable target for measurable residual disease monitoring and the disease is one of the two indications for menin inhibitors.
- Prognostic benefit is lost when FLT3-ITD is co-mutated at high allelic ratio.
- Discovery study; clinical management implications developed over the following decade.