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

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

Noa G Holtzman  1   2 , Michael S Lebowitz  3 , Rima Koka  4 , Maria R Baer  1   5 , Kanam Malhotra  3 , Amir Shahlaee  3 , Hossein A Ghanbari  3 , Søren M Bentzen  1   6 , Ashkan Emadi  1   5   7
Affiliations

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

Noa G Holtzman et al. Front Oncol. .

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.

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Conflict of interest statement

Authors ML, KM and AS were employed by company Sensei Biotherapeutics. ML: Stock ownership in Sensei. AS: Stock ownership in and received consultancy fee from Sensei. HG: Founder and emeritus CSO, Panacea Pharmaceuticals/Sensei Biotherapeutics, Founder/CEO, Athanor Biosciences, MD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ASPH surface expression on myeloblasts and monoblasts. Expression data for the whole patient population showed a ‘mixed population’, i.e. a clustering of patients with low or zero expression mixed with patients with stronger expression, which was used to identify a robust cut-point of 10 MFI (black dashed line) separating high (i.e., positive, red circles) from low (i.e., negative, white circles) mean ASPH expression on myeloblast (x-axis) or monoblast (y-axis) surface.
Figure 2
Figure 2
Event-free survival did not correlate with ASPH status (p=0.87). Blue line represents ASPH- negative AML patients and red line is ASPH-positive AML patients.
Figure 3
Figure 3
Overall survival did not correlate with ASPH status (p=0.169). Blue line represents ASPH-negative AML patients and red line is ASPH-positive AML patients. Patients were censored at the time of death, loss to follow-up, or HSCT.
See this image and copyright information in PMC

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