Efeito citotóxico do composto YM-155 em linhagens derivadas de leucemia linfóide aguda de células T

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that arises from the malignant transformation of T-cell progenitors. Despite the significant progress in current treatment, challenges remain the lifelong morbidity after present chemotherapy regimens and post-relapse survival. Additionally, patients with T-ALL have poor prognosis compared to those with B-cell precursor, consequently, novel therapeutic approaches are still needed to improve the outcome in this cohort. YM-155 is an imidazolium derivative originally discovered as supressant of survivin transcription and has potent antiproliferative effects on a variety of human cancer, but, YM-155 effect in T-ALL cell line is underexplored. Based on this information, the present study aimed to evaluate YM-155 effect on cell lines derived from pediatric T-ALL. The drug exhibited antiproliferative activity and induced apoptosis. JURKAT cells (IC50 value: was 73.11 ± 7.65 nM) was more sensitive to treatment than CCRF-CEM (IC50 value: 2.17 ± 0.08 uM). Moreover, YM- 155 decreased clonogenic capacity and affected cell cycle dynamic. In CCRF- CEM, the treatment induced S phase arrest and, in JURKAT cells, decreased G2/M population and increased sub-G1 fraction. However, in both cell line, inhibition of survivin expression was not observed after treatment with YM-155, as well as the inhibition of VEGF and Bcl-xL genes expression, suggesting that this compound, in p53-deficient T-ALL cell line, is acting independently of survivin and SP-1 transcription factor inhibition. This results reinforcing the likelihood of using YM-155 as a therapeutic approach to combat leukemia and increase knowledge about mechanisms in vitro.