A novel clinically relevant graft-versus-leukemia model in humanized mice.

Bei Jia
Chenchen Zhao
Michael Bayerl
Hiroko Shike
David F Claxton
W Christopher Ehmann
Shin Mineishi
Todd D Schell
Pan Zheng
Yi Zhang
Leonard D. Shultz, The Jackson Laboratory
K Sandeep Prabhu
Robert F Paulson
Hong Zheng

Abstract

The prognosis for acute myeloid leukemia (AML) relapse post allogeneic hematopoietic stem cell transplantation (alloSCT) is dismal. Novel effective treatment is urgently needed. Clinical benefit of alloSCT greatly relies on the graft-versus-leukemia (GVL) effect. The mechanisms that mediate immune escape of leukemia (thus causing GVL failure) remain poorly understood. Studies of human GVL have been hindered by the lack of optimal clinically relevant models. Here, using our large, longitudinal clinical tissue bank that include AML cells and G-CSF mobilized donor hematopoietic stem cells (HSCs), we successfully established a novel GVL model in humanized mice. Donor HSCs were injected into immune-deficient NOD-Cg-Prkdc