Expression of apoptotic miRNAs by cells of the chronic lymphocytic leukemia lineage MEC1 after treatment with Ibrutinib (PCI-32765) and trichostatin A

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5+ B cells in lymphoid organs and peripheral blood. The incidence is high in people over 50 years of age and its prognosis is quite diverse, also affecting treatment. Several therapies are currently in use but, in some cases, there may be resistance and disease relapsing, which demands a search for new alternatives. Several miRNAs, which have the function of regulating messenger RNAs (mRNA), have already been reported with abnormal expression in several types of cancer, including CLL, and may act in the outcome of the disease. The diversity of chromosomal mutations existing in patients with CLL is the main cause of changes in miRNAs and its consequent effect on prognosis. A widely used class of drug is Bruton's Tyrosine Kinase (BTK) inhibitors, such as Ibrutinib (PCI-32765), which induce cell apoptosis by decreasing cell activation. However, there is a high probability of resistance due to a mutation that can occur in the enzyme. Another promising drug class being studied is Histone Deacetylase (HDAC) inhibitors such as Trichostatin A (TSA), which can induce apoptosis by inhibiting the repression of gene transcription made by HDACs, which are at high levels in LLC. Therefore, this project aims to observe the effectiveness of these two treatments in the modulation of apoptotic miRNAs in MEC-1 lineage cells, derived from CLL.