An IDO1-related immune gene signature predicts overall survival in acute myeloid leukemia

Ragaini, S., Wagner, S., Marconi, G., Parisi, S., Sartor, C., Nanni, J., Cristiano, G., Talami, A., Olivi, M., Ocadlikova, D., Ciciarello, M., Corradi, G., Ottaviani, E., Papayannidis, C., Paolini, S., Vadakekolathu, J. ORCID: 0000-0002-2671-4285, Cavo, M., Rutella, S. ORCID: 0000-0003-1970-7375 and Curti, A., 2021. An IDO1-related immune gene signature predicts overall survival in acute myeloid leukemia. Blood Advances. ISSN 2473-9529

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Abstract

The contribution of the bone marrow (BM) immune microenvironment (TME) 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 (IFN)-γ-inducible mediator of immune tolerance. With the aim to develop a prognostic IDO1-based immune gene signature, biological and clinical data of 732 patients with newly diagnosed, non-promyelocytic 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 IDO1low and IDO-1high and between PLXNC1low and PLXNC1 high 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.

Item Type: Journal article
Publication Title: Blood Advances
Creators: Ragaini, S., Wagner, S., Marconi, G., Parisi, S., Sartor, C., Nanni, J., Cristiano, G., Talami, A., Olivi, M., Ocadlikova, D., Ciciarello, M., Corradi, G., Ottaviani, E., Papayannidis, C., Paolini, S., Vadakekolathu, J., Cavo, M., Rutella, S. and Curti, A.
Publisher: American Society of Hematology
Date: 17 September 2021
ISSN: 2473-9529
Identifiers:
NumberType
10.1182/bloodadvances.2021004878DOI
1472844Other
Rights: © 2021 American Society of Hematology
Divisions: Schools > School of Science and Technology
Record created by: Jeremy Silvester
Date Added: 23 Sep 2021 10:21
Last Modified: 07 Oct 2021 14:17
URI: http://irep.ntu.ac.uk/id/eprint/44238

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