NPM1

Is AML NPM1mut a candidate for immune checkpoint inhibition?

On 21st September 2017, in a Letter to the Editor of  Haematologica, Jochen Greiner et al. from the University of Ulm, Germany, reported results of their study which evaluated whether mutated Nucleophosmin 1 (NPM1mut) Acute Myeloid Leukemia (AML) patients might be candidates  for Programmed Death 1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) directed immune checkpoint inhibition.

Peripheral Blood (PB) samples from NPM1mut (n = 15) and NPM1 Wild-Type (NPM1wt [n = 15]) AML patients at diagnosis were assessed for PD-L1 expression in leukemic cells including the Leukemic Stem Cells (LSCs) compartment using flow cytometry and microarray analysis.

The key results of the study were:
  • Median PD-L1 expression in bulk AML cells was significantly higher in NPM1mut patients compared to NPM1wt patients; 1.4% (range, 0.0–8.5%) vs 0.3% (range, 0.0–1.1%) positive cells, P < 0.0001
  • PD-L1 expression was detected significantly at a higher percentage in the LSCs in NPM1mut AML than in NPM1wt AML; 3.6% (range, 0.0–17.2%) vs 0.3% (range, 0.0–3.0%) positive cells, P < 0.001
  • PD-L1 positive LSCs of NPM1mut AML samples had a significant expression of mutant NPM1

In summary, PD-L1 expression was higher in NPM1mut patients particularly in the LSCs compartment compared to NPM1wt AML cases.

The authors concluded by noting that in NPM1mut AML cases, “the immunogenicity of neoantigens derived from the NPM1 mutation and the higher PD-L1 expression constitute a promising target structures for individualized immunotherapeutic approaches”. 

References
  1. Greiner J. et al. Acute Myeloid Leukemia With Mutated Nucleophosmin 1 - An Immunogenic AML Subtype And Potential Candidate For Immune Checkpoint Inhibition. Haematologica. 2017 Sep 21. DOI: 10.3324/haematol.2017.176461. [Epub ahead of print].