@article{Olivia L. Francis_Terry-Ann M. Milford_Shannalee R. Martinez_Ineavely Baez_Jacqueline S. Coats_Karina Mayagoitia_Katherine R. Concepcion_Elizabeth Ginelli_Cornelia Beldiman_Abigail Benitez_Abby J. Weldon_Keshav Arogyaswamy_Parveen Shiraz_Ross Fisher_Christopher L. Morris_Xiao-Bing Zhang_Valeri Filippov_Ben Van Handel_Zheng Ge_Chunhua Song_Sinisa Dovat_Ruijun Jeanna Su_Kimberly J. Payne_2016, place={Pavia, Italy}, title={A novel xenograft model to study the role of TSLP-induced CRLF2 signals in normal and malignant human B lymphopoiesis}, volume={101}, url={https://haematologica.org/article/view/7677}, DOI={10.3324/haematol.2015.125336}, abstractNote={Thymic stromal lymphopoietin (TSLP) stimulates <em>in vitro</em> proliferation of human fetal B-cell precursors. However, its <em>in vivo</em> role during normal human B lymphopoiesis is unknown. Genetic alterations that cause overexpression of its receptor component, cytokine receptor-like factor 2 (CRLF2), lead to high-risk B-cell acute lymphoblastic leukemia implicating this signaling pathway in leukemogenesis. We show that mouse thymic stromal lymphopoietin does not stimulate the downstream pathways (JAK/STAT5 and PI3K/AKT/mTOR) activated by the human cytokine in primary high-risk leukemia with overexpression of the receptor component. Thus, the utility of classic patient-derived xenografts for <em>in vivo</em&gt; studies of this pathway is limited. We engineered xenograft mice to produce human thymic stromal lymphopoietin (+T mice) by injection with stromal cells transduced to express the cytokine. Control (−T) mice were produced using stroma transduced with control vector. Normal levels of human thymic stromal lymphopoietin were achieved in sera of +T mice, but were undetectable in −T mice. Patient-derived xenografts generated from +T as compared to −T mice showed a 3–6-fold increase in normal human B-cell precursors that was maintained through later stages of B-cell development. Gene expression profiles in high-risk B-cell acute lymphoblastic leukemia expanded in +T mice indicate increased mTOR pathway activation and are more similar to the original patient sample than those from −T mice. +T/−T xenografts provide a novel pre-clinical model for understanding this pathway in B lymphopoiesis and identifying treatments for high-risk B-cell acute lymphoblastic leukemia with overexpression of cytokine-like factor receptor 2.}, number={4}, journal={Haematologica}, author={Olivia L. Francis and Terry-Ann M. Milford and Shannalee R. Martinez and Ineavely Baez and Jacqueline S. Coats and Karina Mayagoitia and Katherine R. Concepcion and Elizabeth Ginelli and Cornelia Beldiman and Abigail Benitez and Abby J. Weldon and Keshav Arogyaswamy and Parveen Shiraz and Ross Fisher and Christopher L. Morris and Xiao-Bing Zhang and Valeri Filippov and Ben Van Handel and Zheng Ge and Chunhua Song and Sinisa Dovat and Ruijun Jeanna Su and Kimberly J. Payne}, year={2016}, month={Mar.}, pages={417-426} }