Histamine H2 receptor modulates MRP4/ABCC4 expression in acute myeloid leukemia

MARTÍN ABBA; ANA SAHORES; CARLOS DAVIO; ANTONELA DÍAZ NEBREDA; CARINA SHAYO; NICOLÁS DI SIERVI; ÁNGELA RODRÍGUEZ-GONZÁLEZ

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

SAIC, SAIB, SAB, etc

Acute Myeloid Leukemia (AML) is a heterogeneous hematopoietic disorder where blood precursors lose their ability of normal differentiation and proliferation. Chemotherapy is the first-line treatment, complemented with differentiation therapy and immunotherapy (including histamine and IL-2). In previous studies, we demonstrated the importance of the cAMP pathway in AML differentiation and the role of H2 histamine receptor (H2R), phosphodiesterases and MRP4 (cAMP efflux) in this regulation. cAMP's ability to regulate MRP4 levels was described, as well. The aim of this This study, was aimed to evaluate the modulation of MRP4 expression in leukemic cells treated with histamine, and to test the therapeutical potential of a combined treatment using approach with histamine and a MRP4 inhibitor. In different AML cellular models (U937, HL60, KG1a), Hhistamine and H2 agonist stimulation increased the expression of MRP4 mRNA and protein levels (p