Repositioned to attack CML cells

Eradication of CML stem cells

Bcr-Abl tyrosine kinase inhibitors (TKIs) have become the standard of care for patients with chronic myeloid leukemia (CML). Indeed, patients experience high response rates and long-term survival with continuous TKI treatment. However, TKIs rarely cure CML due to their inability to target CML stem cells. Consequently, CML will soon become the most prevalent leukemia with 100,000 patients in the...

Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC(1280) library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compar...

Novel signaling axis in CML-initiating cells.

T315I+ tyrosine-kinase independent CML cells resistance

Thiopurine Drugs Repositioned as Tyrosinase Inhibitors

Drug repositioning is the application of the existing drugs to new uses and has the potential to reduce the time and cost required for the typical drug discovery process. In this study, we repositioned thiopurine drugs used for the treatment of acute leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two successive oxidations in melanin biosynthesis: the conversions of tyrosine to dih...