Combination of Ethacrynic Acid and ATRA Triggers Differentiation and/or Apoptosis of Acute Myeloid Leukemia Cells through ROS.

Background And Objective: All-trans retinoic acid (ATRA), an effective differentiation inducer, has been applied clinically to treat acute promyelocytic leukemia (APL). Unfortunately, it is not as potent in other kinds of acute myeloid leukemia (AML). Ethacrynic acid (EA), a classical powerful diuretic, can increase reactive oxygen species (ROS) contents, which can assist ATRA in inducing differentiation in AML cells.

Combined Application of Salinomycin and ATRA Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells by Inhibiting WNT/β-Catenin Pathway.

Background And Objective: All-trans retinoic acid (ATRA) is only effective in acute promyelocytic leukemia (APL), but not in other subtype of acute myeloid leukemia (AML). Salinomycin targets tumor cells rather than non-tumorigenic cells, and WNT/β-catenin pathway inhibition is one of the mechanisms of its anti-tumor activity. There is a crosstalk between RA and WNT/β-catenin pathway.

Combination of midostaurin and ATRA exerts dose-dependent dual effects on acute myeloid leukemia cells with wild type FLT3.

Background: Midostaurin combined with chemotherapy is currently used to treat newly diagnosed acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3 (FLT3)-mutations. However, midostaurin acts as an antagonist to some chemotherapeutic agents in leukemia cell lines without FLT3 mutations. All-trans retinoic acid (ATRA) induces apoptosis when used in combination with midostaurin in FLT3-mutated AML cells.