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

Abhishek Mangaonkar, Ashis Kumar Mondal, Sadanand Fulzule, Chetan Pundkar, Eun Jeong Park, Anand Jillella, Vamsi Kota, Hongyan Xu, Natasha Marie Savage, Huidong Shi, David H Munn, Ravindra Bharat Kolhe

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Abstract

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.

Original languageEnglish (US)
Article number12892
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Acute Myeloid Leukemia
Mortality
Messenger RNA
Bone Marrow
Kynurenine
Immune Tolerance
Cytogenetics

ASJC Scopus subject areas

  • General

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A novel immunohistochemical score to predict early mortality in acute myeloid leukemia patients based on indoleamine 2,3 dioxygenase expression. / Mangaonkar, Abhishek; Mondal, Ashis Kumar; Fulzule, Sadanand; Pundkar, Chetan; Park, Eun Jeong; Jillella, Anand; Kota, Vamsi; Xu, Hongyan; Savage, Natasha Marie; Shi, Huidong; Munn, David H; Kolhe, Ravindra Bharat.

In: Scientific Reports, Vol. 7, No. 1, 12892, 01.12.2017.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Jillella, Anand

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AU - Xu, Hongyan

AU - Savage, Natasha Marie

AU - Shi, Huidong

AU - Munn, David H

AU - Kolhe, Ravindra Bharat

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