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

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 mono...

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Main Authors: Deepti Reddi, Brandon W. Seaton, David Woolston, Lauri Aicher, Luke D. Monroe, Zhengwei J. Mao, Jill C. Harrell, Jerald P. Radich, Anjali Advani, Nikolaos Papadantonakis, Cecilia C. S. Yeung
Format: Article
Language:English
Published: Nature Portfolio 2022-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-09697-6
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author Deepti Reddi
Brandon W. Seaton
David Woolston
Lauri Aicher
Luke D. Monroe
Zhengwei J. Mao
Jill C. Harrell
Jerald P. Radich
Anjali Advani
Nikolaos Papadantonakis
Cecilia C. S. Yeung
author_facet Deepti Reddi
Brandon W. Seaton
David Woolston
Lauri Aicher
Luke D. Monroe
Zhengwei J. Mao
Jill C. Harrell
Jerald P. Radich
Anjali Advani
Nikolaos Papadantonakis
Cecilia C. S. Yeung
author_sort Deepti Reddi
collection DOAJ
description 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.
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spelling doaj.art-d9f0d764d2d24b37b37880b7ec019bff2022-12-21T17:57:35ZengNature PortfolioScientific Reports2045-23222022-04-011211810.1038/s41598-022-09697-6AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarkerDeepti Reddi0Brandon W. Seaton1David Woolston2Lauri Aicher3Luke D. Monroe4Zhengwei J. Mao5Jill C. Harrell6Jerald P. Radich7Anjali Advani8Nikolaos Papadantonakis9Cecilia C. S. Yeung10Department of Laboratory Medicine and Pathology, University of WashingtonFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterHematology and Medical Oncology, Cleveland ClinicWinship Cancer Institute of Emory UniversityDepartment of Laboratory Medicine and Pathology, University of WashingtonAbstract 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.https://doi.org/10.1038/s41598-022-09697-6
spellingShingle Deepti Reddi
Brandon W. Seaton
David Woolston
Lauri Aicher
Luke D. Monroe
Zhengwei J. Mao
Jill C. Harrell
Jerald P. Radich
Anjali Advani
Nikolaos Papadantonakis
Cecilia C. S. Yeung
AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
Scientific Reports
title AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
title_full AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
title_fullStr AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
title_full_unstemmed AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
title_short AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
title_sort akr1c3 expression in t acute lymphoblastic leukemia lymphoma for clinical use as a biomarker
url https://doi.org/10.1038/s41598-022-09697-6
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