Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target

BackgroundAspartate β-hydroxylase (ASPH) is an embryonic transmembrane protein aberrantly upregulated in cancer cells, associated with malignant transformation and, in some reports, with poor clinical prognosis.ObjectiveTo report the expression patterns of ASPH in acute myeloid leukemia (AML).Method...

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Main Authors: Noa G. Holtzman, Michael S. Lebowitz, Rima Koka, Maria R. Baer, Kanam Malhotra, Amir Shahlaee, Hossein A. Ghanbari, Søren M. Bentzen, Ashkan Emadi
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.783744/full
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author Noa G. Holtzman
Noa G. Holtzman
Michael S. Lebowitz
Rima Koka
Maria R. Baer
Maria R. Baer
Kanam Malhotra
Amir Shahlaee
Hossein A. Ghanbari
Søren M. Bentzen
Søren M. Bentzen
Ashkan Emadi
Ashkan Emadi
Ashkan Emadi
author_facet Noa G. Holtzman
Noa G. Holtzman
Michael S. Lebowitz
Rima Koka
Maria R. Baer
Maria R. Baer
Kanam Malhotra
Amir Shahlaee
Hossein A. Ghanbari
Søren M. Bentzen
Søren M. Bentzen
Ashkan Emadi
Ashkan Emadi
Ashkan Emadi
author_sort Noa G. Holtzman
collection DOAJ
description BackgroundAspartate β-hydroxylase (ASPH) is an embryonic transmembrane protein aberrantly upregulated in cancer cells, associated with malignant transformation and, in some reports, with poor clinical prognosis.ObjectiveTo report the expression patterns of ASPH in acute myeloid leukemia (AML).MethodsCell surface expression of ASPH was measured via 8-color multiparameter flow cytometry in 41 AML patient samples (31 bone marrow, 10 blood) using fluorescein isothiocyanate (FITC)-conjugated anti-ASPH antibody, SNS-622. A mean fluorescent intensity (MFI) of 10 was used as a cutoff for ASPH surface expression positivity. Data regarding patient and disease characteristics were collected.ResultsASPH surface expression was found on AML blasts in 16 samples (39%). Higher ASPH expression was seen in myeloblasts of African American patients (p=0.02), but no correlation was found between ASPH expression and other patient or disease characteristics. No association was found between ASPH status and CR rate (p=0.53), EFS (p=0.87), or OS (p=0.17).ConclusionsASPH is expressed on blasts in approximately 40% of AML cases, and may serve as a new therapeutically targetable leukemia-associated antigen.
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spelling doaj.art-f86fb60e39bc4aa5ab5969a96ee00ea42022-12-21T19:34:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.783744783744Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic TargetNoa G. Holtzman0Noa G. Holtzman1Michael S. Lebowitz2Rima Koka3Maria R. Baer4Maria R. Baer5Kanam Malhotra6Amir Shahlaee7Hossein A. Ghanbari8Søren M. Bentzen9Søren M. Bentzen10Ashkan Emadi11Ashkan Emadi12Ashkan Emadi13Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United StatesImmune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesSensei Biotherapeutics Inc., Gaithersburg, MD, United StatesDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD, United StatesMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, United StatesSensei Biotherapeutics Inc., Gaithersburg, MD, United StatesSensei Biotherapeutics Inc., Gaithersburg, MD, United StatesSensei Biotherapeutics Inc., Gaithersburg, MD, United StatesMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Epidemiology and Biostatistics, University of Maryland School of Medicine, Baltimore, MD, United StatesMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United StatesBackgroundAspartate β-hydroxylase (ASPH) is an embryonic transmembrane protein aberrantly upregulated in cancer cells, associated with malignant transformation and, in some reports, with poor clinical prognosis.ObjectiveTo report the expression patterns of ASPH in acute myeloid leukemia (AML).MethodsCell surface expression of ASPH was measured via 8-color multiparameter flow cytometry in 41 AML patient samples (31 bone marrow, 10 blood) using fluorescein isothiocyanate (FITC)-conjugated anti-ASPH antibody, SNS-622. A mean fluorescent intensity (MFI) of 10 was used as a cutoff for ASPH surface expression positivity. Data regarding patient and disease characteristics were collected.ResultsASPH surface expression was found on AML blasts in 16 samples (39%). Higher ASPH expression was seen in myeloblasts of African American patients (p=0.02), but no correlation was found between ASPH expression and other patient or disease characteristics. No association was found between ASPH status and CR rate (p=0.53), EFS (p=0.87), or OS (p=0.17).ConclusionsASPH is expressed on blasts in approximately 40% of AML cases, and may serve as a new therapeutically targetable leukemia-associated antigen.https://www.frontiersin.org/articles/10.3389/fonc.2021.783744/fullleukemiamyeloidmyeloblastsASPHleukemia-associated antigen
spellingShingle Noa G. Holtzman
Noa G. Holtzman
Michael S. Lebowitz
Rima Koka
Maria R. Baer
Maria R. Baer
Kanam Malhotra
Amir Shahlaee
Hossein A. Ghanbari
Søren M. Bentzen
Søren M. Bentzen
Ashkan Emadi
Ashkan Emadi
Ashkan Emadi
Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target
Frontiers in Oncology
leukemia
myeloid
myeloblasts
ASPH
leukemia-associated antigen
title Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target
title_full Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target
title_fullStr Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target
title_full_unstemmed Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target
title_short Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target
title_sort aspartate β hydroxylase asph expression in acute myeloid leukemia a potential novel therapeutic target
topic leukemia
myeloid
myeloblasts
ASPH
leukemia-associated antigen
url https://www.frontiersin.org/articles/10.3389/fonc.2021.783744/full
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