Hepatic leukemia-associated macrophages exhibit a pro-inflammatory phenotype in Notch1-induced acute T cell leukemia |
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| Authors: | Xiao Yang Wenli Feng Rong Wang Feifei Yang Lina Wang Shayan Chen Chong Chen Qian Ren Guoguang Zheng |
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| Institution: | 1. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China;2. Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China |
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| Abstract: | Tumor-associated macrophages (TAMs) are well accepted and the pathological role of macrophages in hematopoietic malignancies have been proposed. Hepatomegaly is frequently observed in T cell acute lymphoblastic leukemia (T-ALL) patients with poor prognosis. However, the role of leukemia-associated macrophages (LAMs) in hepatic microenvironment remains unclear. Here, the characteristics of hepatic LAMs (H-LAMs) were studied in Notch1 induced T-ALL model. Increase in proportion and absolute counts of H-LAMs was detected with infiltration of inflammatory cells. Furthermore, H-LAMs exhibited a more M1-like phenotype distinct from that of TAMs in hepatocellular carcinoma and LAMs from BM or spleen in leukemia. Moreover, H-LAMs expressed increased level of cytokines in charge of recruiting inflammatory cells, which contributed to pro-inflammatory hepatic microenvironment. |
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| Keywords: | T-ALL T cell acute lymphoblastic leukemia H-LAMs hepatic leukemia-associated macrophages TAMs tumor-associated macrophages HCC hepatocellular carcinoma BM bone marrow SP spleen HSC/HPCs hematopoietic stem cells/hematopoietic progenitor cells Hepatic leukemia-associated macrophages Hepatomegaly M1 polarization iNOS |
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