@article{d7e636f0f19947f09f94adc8b54e96c5,
title = "A novel clinically relevant graft-versus-leukemia model in humanized mice",
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-PrkdcscidIL2rgtm1Wjl/SzJ (NSG) mice to build humanized mice. Immune reconstitution in these mice recapitulated some clinical scenario in the patient who received the corresponding HSCs. Allogeneic but HLA partially matched patient-derived AML cells were successfully engrafted in these humanized mice. Importantly, we observed a significantly reduced (yet incomplete elimination of) leukemia growth in humanized mice compared with that in control NSG mice, demonstrating a functional (but defective) GVL effect. Thus, for the first time, we established a novel humanized mouse model that can be used for studying human GVL responses against human AML cells in vivo. This novel clinically relevant model provides a valuable platform for investigating the mechanisms of human GVL and development of effective leukemia treatments.",
author = "Bei Jia and Chenchen Zhao and Michael Bayerl and Hiroko Shike and Claxton, {David F.} and Ehmann, {W. Christopher} and Shin Mineishi and Schell, {Todd D.} and Pan Zheng and Yi Zhang and Shultz, {Leonard D.} and Prabhu, {K. Sandeep} and Paulson, {Robert F.} and Hong Zheng",
note = "Funding Information: We thank all our patients for their trust, understanding, and willingness to provide their blood samples for our research. This work was supported by the American Society of Hematology Scholar Award Grant, Penn State Cancer Institute Funds, the Penn State University Enhancing Health Initiative, the Kiesendahl Endowment funding, the G.R. Sponaugle Employee Cancer Research Fund, the Vernon M. and Jolene E. Chinchilli Family Endowment fund for Cancer Research, and NIH grants CA034196 (L.D.S.). This project is funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions. We would like to thank the technical support of Jade Vogel, Nate Sheaffer, and Joe Bednarczyk from the Flow Cytometry Core Facility of the Penn State College of Medicine. Ellen Mullady and Dr. Hannah Atkins from the Comparative Medicine of Penn State College of Medicine kindly provided technique support for CBC test. Funding Information: We thank all our patients for their trust, understanding, and willingness to provide their blood samples for our research. This work was supported by the American Society of Hematology Scholar Award Grant, Penn State Cancer Institute Funds, the Penn State University Enhancing Health Initiative, the Kiesendahl Endowment funding, the G.R. Sponaugle Employee Cancer Research Fund, the Vernon M. and Jolene E. Chinchilli Family Endowment fund for Cancer Research, and NIH grants CA034196 (L.D.S.). This project is funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions. We would like to thank the technical support of Jade Vogel, Nate Sheaffer, and Joe Bednarczyk from the Flow Cytometry Core Facility of the Penn State College of Medicine. Ellen Mullady and Dr. Hannah Atkins from the Comparative Medicine of Penn State College of Medicine kindly provided technique support for CBC test. Publisher Copyright: {\textcopyright}2021 Society for Leukocyte Biology",
year = "2022",
month = feb,
doi = "10.1002/JLB.5AB0820-542RR",
language = "English (US)",
volume = "111",
pages = "427--437",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "Oxford University Press",
number = "2",
}