Obtaining and characterizing an Imatinib resistant K562 derivate CML cell line: Ki562. Effect of 4-methylumbelliferone on metabolic activity and CD44 expression

DIAZ M; PIBUEL M; ÁLVAREZ E; HAJOS SE; SARANGO ORTEGA YB; NORIEGA MF; FONTECHA MB; LARRIPA IB; LOMPARDIA S; MARIA DEL ROSARIO ANADON; POODTS D; AMOIA S; FUNDIA AF

Ciudad De Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencia; 2020

Sociedad Argentina De Investigación Clínica

CML is a myeloproliferative neoplasia whose first-line therapy are BCR-ABL inhibitors such as Imatinib (IM). CD44 levels correlates with bad response to therapy. Previously, we demonstrated that hyaluronic acid (HA) abrogates IM-induced senescence, while the inhibition of its synthesis with 4-methylumbelliferone (4MU) has a synergistic effect with IM on CML cells growth. The aim of this work was to obtain an IM resistant K562 derivate cell line and to study the resistance mechanisms involved, as well as, the effect of 4MU treatment. The Ki562 cells were obtained after culturing K562 cells with increasing doses of IM from 0.1µM up to 1µM. Control cells derivate of K562, Ko562, were kept in culture presenting the same aging but, without selection pressure of IM. None of these cells showed efflux pump activity (determined by flow cytometry, FC). Both cell lines had a similar frequency of the F359I mutation (evaluated by DNA sequencing). However, Ki562 cells showed higher levels of BCR-ABL than Ko562 cells (evaluated by RT-PCR and WB, p