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Mesothelin Under Study as Diagnostic and Therapeutic Target in AML

By: Joseph Fanelli
Posted: Wednesday, June 30, 2021

According to findings presented in Blood Advances, the cell-surface protein mesothelin seems to be expressed in a large number of patients with acute myeloid leukemia (AML) and has potential as a diagnostic and therapeutic target. Soheil Meshinchi, MD, PhD, of The Fred Hutchinson Cancer Research Center, Seattle, and colleagues concluded that mesothelin-directed therapeutic strategies, including antibody-drug conjugates, are worthy of further clinical investigations based on these results.

“Mesothelin expression is observed across the age spectrum in AML but is absent from normal hematopoietic precursors,” the authors said. “The progress made in mesothelin-positive solid tumors with an array of targeted and immunotherapeutic strategies positions mesothelin to be an impactful new therapeutic target in AML.”

The authors collected diagnostic samples from 2,051 pediatric patients with de novo acute myeloid leukemia (aged 1 week to 29.6 years). The expression profiles of these patients were compared with normal marrow specimens.

The protein mesothelin was “highly overexpressed” in 36% of the patients with AML and “virtually absent” in the normal marrow, according to the researchers. Additionally, mesothelin was highly expressed in patients with KMT2A rearrangements, core-binding factor fusions, and extramedullary disease.

When evaluating in vitro and in vivo preclinical efficacy of the mesothelin-directed antibody-drug conjugate anetumab ravtansine, the authors found that treatment resulted in target-dependent cytotoxicity in patients with mesothelin-positive AML. “Antigen load at diagnosis due to a high white blood cell count is a concern for antibody-drug conjugates; thus, they may be most effective when administered as combination therapy in hematologic malignancies,” the authors added.

Disclosure: For a full disclosure of the study authors,  visit ashpublications.org.


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