Induction and Therapeutic Targeting of Human NPM1c+ Myeloid Leukemia in the Presence of Autologous Immune System in Mice

Purpose: To understand the molecular mechanisms underlying NPM1c-mediated tumorigenesis by comparing the transcriptome of de novo generated bulk human leukemic cells and leukemic stem cells Overall design: Human hematopoietic stem/progenitor cells (HSPC) are transduced with lentiviruses expressing a mutated form of Nucleophosmin (NPM1c). Following engraftment into immunodeficient mice, transduced HSPCs give rise to human myeloid leukemia whereas untransduced HSPCs give rise to human immune cells in the same mice. The de novo AML, with CD123+ leukemic stem cells (LSC), resembles NPM1c+ AML from patients.

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Kaur M, Drake AC, Hu G, Rudnick S, Chen Q, Phennicie R, Attar R, Nemeth J, Gaudet F, Chen J