AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker

• Type of Material: Article
• Authors: Deepti Reddi, University of Washington; Brandon W Seaton, Fred Hutchinson Cancer Research Center; David Woolston, Fred Hutchinson Cancer Research Center; Lauri Aicher, Fred Hutchinson Cancer Research Center; Luke D Monroe, Fred Hutchinson Cancer Research Center; Zhengwei J Mao, Fred Hutchinson Cancer Research Center; Jill C Harrell, Fred Hutchinson Cancer Research Center; Jerald P Radich, Fred Hutchinson Cancer Research Center; Anjali Advani, Cleveland Clin; Nikolaos Papadantonakis, Emory University; Cecilia CS Yeung, University of Washington
• Language: English
• Date: 2022-04-06
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-022-09697-6
• Title of Journal or Parent Work: SCIENTIFIC REPORTS
• Volume: 12
• Issue: 1
• Start Page: 5809
• End Page: 5809
• Grant/Funding Information: The preliminary research work was funded by the Hope foundation.
• Keywords: Science & Technology - Other Topics; KETO REDUCTASE AKR1C3; PRODRUG PR-104A; Multidisciplinary Sciences; Science & Technology; LEUKEMIA
• Research Categories: Health Sciences, Oncology

Abstract

To investigate aldo–keto reductase 1C3 (AKR1C3) expression in T and B acute lymphoblastic leukemia/lymphoma (ALL) patients. Three commercial antibodies were evaluated for AKR1C3 immunohistochemistry (IHC) staining performance: Polyclonal Thermofisher scientific (Clone#PA523667), rabbit monoclonal Abcam [EPR16726] (ab209899) and Sigma/Millipore anti-AKR1C3 antibody, mouse monoclonal, clone NP6.G6.A6, purified from hybridoma cell culture. Initial optimization was performed on cell line controls: HCT116 (negative control); genetically modified cell line HCT116 with AKR1C3 overexpression; Nalm and TF1 cell lines. Twenty normal bone marrows from archival B and T-ALL patient samples were subsequently examined. AKR1C3 expression levels in these samples were evaluated by immunohistochemistry, Protein Wes and quantitative RT-PCR. Sigma/Millipore Anti-AKR1C3 antibody (mouse monoclonal, clone NP6.G6.A6) showed higher specificity compared to rabbit polyclonal antibody by immunohistochemistry. H-score was used to quantify percent of nuclear immunoreactivity for AKR1C3 with varying disease involvement. T-ALL samples had a higher H-score (172–190) compared to B-ALL cases (H-score, 30–160). The AKR1C3 expression in peripheral blood by Protein Wes and RT-qPCR showed concordance in relapsed/refractory and/or minimal residual T-ALL cases. Sigma/Millipore Anti-AKR1C3 antibody and mouse monoclonal, clone NP6.G6.A6 can be used to aid in AKR1C expression of T-ALL and in cases of relapsed/refractory and/or minimal residual disease.