Effect of histamine on the induction of differentiation/apoptosis by MRP4/ABCC4 inhibitors in AML cells: ceefourin-1 evaluation.

SAHORES A; RODRIGUEZ GONZALEZ ANGELA; YANEFF A; MAY M.; GOMEZ NATALIA; CARLOS DAVIO; CARINA SHAYO

Congreso; LXVI Reunión Científica anual de la Sociedad Argentina de Investigación Clínica; 2021

SAIC

We previously described that both, the cAMP transporter MRP4 and the histamine H2 receptor, are molecular targets for Acute Myeloid Leukemia (AML) differentiation therapy. Increased intracellular cAMP concentrations play an important role in leukemic cell maturation, proliferation, and apoptosis. In the present study, we analyzed the ability of histamine (HIST), in combination with MRP inhibitors, to induce AML cell differentiation/apoptosis, and made special made in ceefourin-1. We first evaluated the effect of 100µM HIST on the induction of cell differentiation upon treatment with MRP4 inhibitors (500µM probenecid, 25µM MK571, or 25µM ceefourin-1) in AML cells lines, determined by the expression of CD14 (FACS), CD88 (western blot), and cell morphology (MGG staining). The combined treatment of probenecid or MK571 with HIST significantly increased the differentiation markers (p