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

Noa G Holtzman; Michael S Lebowitz; Rima Koka; Maria R Baer; Kanam Malhotra; Amir Shahlaee; Hossein A Ghanbari; Søren M Bentzen; Ashkan Emadi

doi:10.3389/fonc.2021.783744

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

Front Oncol. 2021 Dec 22:11:783744. doi: 10.3389/fonc.2021.783744. eCollection 2021.

Authors

Noa G Holtzman^{1

2}, Michael S Lebowitz³, Rima Koka⁴, Maria R Baer^{1

5}, Kanam Malhotra³, Amir Shahlaee³, Hossein A Ghanbari³, Søren M Bentzen^{1

6}, Ashkan Emadi^{1

5

7}

Affiliations

¹ Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States.
² Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
³ Sensei Biotherapeutics Inc., Gaithersburg, MD, United States.
⁴ Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States.
⁵ Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
⁶ Department of Epidemiology and Biostatistics, University of Maryland School of Medicine, Baltimore, MD, United States.
⁷ Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United States.

Abstract

Background: Aspartate 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.

Objective: To report the expression patterns of ASPH in acute myeloid leukemia (AML).

Methods: Cell 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.

Results: ASPH 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).

Conclusions: ASPH is expressed on blasts in approximately 40% of AML cases, and may serve as a new therapeutically targetable leukemia-associated antigen.

Keywords: ASPH; leukemia; leukemia-associated antigen; myeloblasts; myeloid.