A novel immunohistochemical score to predict early mortality in acute myeloid leukemia patients based on indoleamine 2,3 dioxygenase expression

• Published in: Scientific reports Vol. 7; no. 1; pp. 12892 - 7
• Main Authors: Mangaonkar, Abhishek, Mondal, Ashis Kumar, Fulzule, Sadanand, Pundkar, Chetan, Park, Eun Jeong, Jillella, Anand, Kota, Vamsi, Xu, Hongyan, Savage, Natasha M., Shi, Huidong, Munn, David, Kolhe, Ravindra
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.10.2017; Nature Publishing Group
• Subjects: 631/250/2520; 631/67/580/1884/2323; 692/4028/67/1990/283/1897; 82/51; Acute myeloid leukemia; Bone marrow; Children; Clinical trials; Cytogenetics; Dioxygenase; Gene expression; Humanities and Social Sciences; Immunohistochemistry; Immunological tolerance; Leukemia; Mortality; multidisciplinary; Myeloid leukemia; Science; Science (multidisciplinary); Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-12940-0

Indoleamine 2,3 dioxygenase-1 (IDO-1) is an enzyme in the kynurenine pathway which augments tumor-induced immune tolerance. Previous studies in childhood acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA expression with outcomes. The aim of our study was to develop a practical and objective immunohistochemical technique to quantify IDO-1 expression on diagnostic bone marrow biopsies of AML patients in order to facilitate its use in routine clinical practice. IDO-1 mRNA was extracted from diagnostic bone marrow specimens from 29 AML patients. IDO-1 protein expression was assessed in 40 cases via immunohistochemistry and quantified by a novel ‘composite IDO-1 score’. In a univariate analysis, higher age (p = 0.0018), male gender (p = 0.019), high risk cytogenetics (p = 0.002), higher IDO-1 mRNA (p = 0.005), higher composite IDO-1 score (p < 0.0001) and not undergoing allogeneic stem cell transplant (SCT, p = 0.0005) predicted poor overall survival. In a multivariate model that included the aforementioned variables, higher composite IDO-1 score (p = 0.007) and not undergoing allogeneic SCT (p = 0.007) was found to significantly predict poor outcomes. Further, patients who failed induction had higher composite IDO-1 score (p = 0.01). In conclusion, ‘composite IDO-1 score’ is a prognostic tool that can help identify a certain subset of AML patients with ‘early mortality’. This unique subset of patients can potentially benefit from specific IDO-1 inhibitor therapy, currently in clinical trials.