Site Editor

Rebecca Olin, MD, MS

Advertisement
Advertisement

Validating NMT Inhibition as Novel Therapeutic Strategy for AML

By: Joseph Fanelli
Posted: Tuesday, May 3, 2022

N-myristoyltransferase (NMT) inhibition therapy may prove to be an effective treatment for patients with acute myeloid leukemia (AML), according to findings presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5662). High doses of the cellular enzyme NMT1 and low doses of NMT2 were found to be associated with reduced overall and event-free survival in this patient population, according to Luc Berthiaume, PhD, of the University of Alberta, Edmonton, Canada, and colleagues.

The authors analyzed data from The Cancer Genome Atlas (TCGA) transcriptome database and monitored the effects of the pan-NMT inhibitor PCLX-001. The inhibitor recently entered human clinical trials as a once-daily oral therapy for relapsed and refractory B-cell non-Hodgkin lymphoma and advanced solid malignancies.

From the TCGA transcriptome database, the authors found that high NMT1 expression—but not NMT2 expression—was associated with proliferative gene sets in AML cell lines. AML cell lines treated with PCLX-001 demonstrated a significant reduction in the total of protein myristoylation, reduced levels of Src family kinase proteins, and Src family kinase phosphorylation, as well as a significant increase in endoplasmic reticulum stress marker binding immunoglobulin protein and caspase-3 cleavage.

Treatment with PCLX-001 induced apoptosis in AML cell lines and patient blasts at concentrations that spared large proportions of peripheral blood lymphocytes and monocytes from healthy individuals, the authors explained. In addition, PCLX-001 monotherapy had dose-dependent anticancer activity in an AML MV-4-11 cell line–derived xenograft.

In tail vein–injected patient-derived xenograft models, PCLX-001 treatment resulted in up to 95% reduction in human CD45-positive cells in peripheral blood and bone marrow. The treatment preferentially targeted AML cells, inducing apoptosis and reducing leukemic burden, the authors concluded.

Disclosure: For a full disclosure of the study authors, visit abstractsonline.com.


By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.