Melatonin promotes differentiation and apoptosis of AML1-ETO-positive cells

Introduction: Acute Myeloid Leukemia 1-Eight-Twenty-One (AML1-ETO) is an oncogenic fusion protein that causes acute myeloid leukemia. We examined the effects of melatonin on AML1-ETO by investigating cell differentiation, Apoptosis, and degradation in leukemia cell lines.

Method: We evaluated Kasumi-1, U937T, and primary acute myeloid leukemia (AML1-ETO-positive) cell proliferation by Cell Counting Kit-8 assay. Flow cytometry and western blotting were used to evaluate CD11b/CD14 levels (differentiation biomarkers) and the AML1-ETO protein degradation pathway, respectively. CM-Dil-labeled Kasumi-1 cells were also injected into zebrafish embryos to determine the effects of melatonin on vascular proliferation and development and to evaluate the combined effects of melatonin and common chemotherapeutic agents.

Results: AML1-ETO-positive acute myeloid leukemia cells were more sensitive to melatonin than AML1-ETO-negative cells. Melatonin increased Apoptosis and CD11b/CD14 expression in AML1-ETO-positive cells and decreased the nuclear/cytoplasmic ratio, together suggesting that melatonin induced cell differentiation. Mechanistically, melatonin degraded AML1-ETO by activating the Caspase-3 pathway and regulating the mRNA levels of AML1-ETO downstream genes. Melatonin reduced the number of neovessels in Kasumi-1-injected zebrafish, suggesting that melatonin inhibits cell proliferation in vivo. Finally, combining drugs with melatonin inhibited cell viability.

Discussion: Melatonin is a potential compound for the treatment of AML1-ETO-positive acute myeloid leukemia.

Acute myeloid leukemia; Leukemia cell line; Melatonin; Oncogenic fusion protein; Zebrafish.