Study of potential therapies against acute myeloid leukaemia (transfer to Tromsø)

This is an application for extension of the FOTS8660. We will use the number of animals left to use from the total of 800 approved previously: 600. Our working conditions split in two labs make it very challenging to keep time frames. The aim of this proyect is to study potential new therapies for the treatment of Acute Myeloid Leukemia (AML). For this purpose, circulating AML cells obtained from patients, will be xenotransplanted in immunodeficient NSG/NSG-SGM3 mice (Schultz et al, see attached). CD34+ cells from healthy donors will be used as control. Prior to transplantation, animals need to be preconditioned through irradiation. Total whole body irradiation is used in the field of blood stem cell function and cancer (for more information: http://www.bu.edu/orccommittees/iacuc/policies-and-guidelines/irradiation-of-rodents/). It allows to kill proliferating blood cells without significant damage of resting tissues. In this study, mice will receive a single 2Gy dose (sublethal). This low level of irradiation does not induce bone marrow depletion, thus no adverse symtoms are expected. This sublethal dose increases the amount of factors released by the bone marrow niche allowing the engragment of transplanted cells and their proliferation. Mice will be transplanted after irradiation and will be divided into different treated groups (5 different drugs, 600 mice in total) and will be monitored over time to check disease progression for 6 months, correlating with changes in the bone marrow microenvironment. We will use Patient-derived AML models, and receive already transplanted Mice if needed, and NSG kit W41/W41 that do not require irradiation to condition the bone marrow. Mice will be used in the most efficient way and numbers are kept to minimum. It is not the goal of this study to analyze terminal stages but provide a novel platform for more efficient therapies against AML, a highly aggressive human disease that may affect children as well. The project end will be 01.09.2024.