Expression differences of miR-142-5p between treatment-naïve chronic myeloid leukemia patients responding and non-responding to imatinib therapy suggest a link to oncogenic ABL2, SRI, cKIT and MCL1 signaling pathways critical for development of therapy resistance.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by constitutive activity of the tyrosine kinase BCR-ABL1. Although the introduction of tyrosine kinase inhibitors (TKIs) has substantially improved patients' prognosis, drug resistance remains one of the major challenges in CML therapy. MicroRNAs (miRNAs), a class of short non-coding RNAs acting as post-transcriptional regulators, are implicated in CML progression and drug resistance.

Alternative Polyadenylation of ABC Transporters of the C-Family (ABCC1, ABCC2, ABCC3) and Implications on Posttranscriptional Micro-RNA Regulation.

ATP-binding cassette (ABC) transporters represent a large group of efflux pumps that are strongly involved in the pharmacokinetics of various drugs and nutrient distribution. It was recently shown that micro-RNAs (miRNAs) may significantly alter their expression as proven, e.g.

MicroRNA-212/ABCG2-axis contributes to development of imatinib-resistance in leukemic cells.

BCR-ABL-independent resistance against tyrosine kinase inhibitor is an emerging problem in therapy of chronic myeloid leukemia. Such drug resistance can be linked to dysregulation of ATP-binding cassette (ABC)-transporters leading to increased tyrosine kinase inhibitor efflux, potentially caused by changes in microRNA expression or DNA-methylation. In an -imatinib-resistance model using K-562 cells, microRNA-212 was found to be dysregulated and inversely correlated to ABC-transporter ABCG2 expression, targeting its 3'-UTR.

OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics.

Length variants of the ABCB1 3'-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance.

Aim: To identify the exact length and possible length variations of the ABCB1 3'-UTR as important regulatory site for miRNA interaction of this drug transporter and its possible contribution to drug resistance.

Materials & Methods: 3'-RACE and various standard PCR experiments were performed using cDNA of different human cell lines and liver tissue. The abundance of 3'-UTR fragments was analyzed using quantitative RT-PCR.