A Preclinical Model of Human Acute Myeloid Leukemia with an Autologous Immune System for Studying Mechanisms of Tumorigenesis and Immunotherapy

Next generation sequencing of bulk leukemic and leukemic stem cells in de novo human AML driven by NPM1c. Data revelas co-operating pathways in NPM1c tumorigenesis. Overall design: Three AML humanized mice generated from 3 independent human hematopoietic stem cell transductions with NPM1c were used for this analysis. Bone marrow cells from moribund mice were harvested and labeled with anti-CD123 and anti-CD33 antibodies followed by cell sorting with the ARIA sorter. GFP expression, a surrogate for NPM1c expression, was also used as a parameter for sorting. 2 populations of cells were sorted from each bone marrow samples: i) Bulk leukemic cells which were GFP+ and CD33+, and ii) Leukemic stem cells which were GFP+, CD33+ and CD123+