The contribution of the bone marrow (BM) immune microenvironment to acute 
myeloid leukemia (AML) development is well-known, but its prognostic 
significance is still elusive. Indoleamine 2,3-dioxygenase 1 (IDO1), which is 
negatively regulated by the BIN1 proto-oncogene, is an interferon-γ-inducible 
mediator of immune tolerance. With the aim to develop a prognostic IDO1-based 
immune gene signature, biological and clinical data of 982 patients with newly 
diagnosed, nonpromyelocytic AML were retrieved from public datasets and analyzed 
using established computational pipelines. Targeted transcriptomic profiles of 
24 diagnostic BM samples were analyzed using the NanoString's nCounter platform. 
BIN1 and IDO1 were inversely correlated and individually predicted overall 
survival. PLXNC1, a semaphorin receptor involved in inflammation and immune 
response, was the IDO1-interacting gene retaining the strongest prognostic 
value. The incorporation of PLXNC1 into the 2-gene IDO1-BIN1 score gave rise to 
a powerful immune gene signature predicting survival, especially in patients 
receiving chemotherapy. The top differentially expressed genes between 
IDO1lowand IDO-1high and between PLXNC1lowand PLXNC1high cases further improved 
the prognostic value of IDO1 providing a 7- and 10-gene immune signature, highly 
predictive of survival and correlating with AML mutational status at diagnosis. 
Taken together, our data indicate that IDO1 is pivotal for the construction of 
an immune gene signature predictive of survival in AML patients. Given the 
emerging role of immunotherapies for AML, our findings support the incorporation 
of immune biomarkers into current AML classification and prognostication 
algorithms.