title: Organ-specific microenvironment modifies diverse functional and phenotypic characteristics of leukemia-associated macrophages in mouse T cell acute lymphoblastic leukemia.
abstract: Tumor-associated macrophages are widely studied in solid tumors. The distribution of macrophages in lymph node samples was found to be associated with the prognosis of lymphoma patients. However, the role of macrophages in leukemia and their functional and phenotypic characteristics in hematopoietic malignancies have not been defined. In this study, we examined the distribution and functional and phenotypic characteristics of macrophages in a Notch1-induced mouse model of T cell acute lymphoblastic leukemia (T-ALL). The distribution of macrophages in bone marrow (BM) and spleen, which are proposed as BM and spleen leukemia-associated macrophages (LAMs), were different during the development of leukemia. LAMs stimulated the proliferation of T-ALL cells and had higher migration activity. RNA-sequencing analysis revealed that gene expression profiles of BM and spleen LAMs showed considerable differences. RT-PCR analysis showed that LAMs expressed both M1- and M2-associated phenotypic genes, but they expressed much lower levels of TGF-β1, VEGF-A, and CSF-1 than did tumor-associated macrophages from B16 melanoma. Furthermore, spleen LAMs more potently stimulated the proliferation of T-ALL cells compared with BM LAMs. Moreover, LAMs could be subdivided into M1-like (CD206(-)) and M2-like (CD206(+)) groups. Both CD206(+) and CD206(-) LAMs stimulated the proliferation of T-ALL cells, although CD206(+) LAMs expressed higher levels of most M1- and M2-associated genes. These results suggested the functional and phenotypic characteristics of LAMs, which were modified by organ specific microenvironments. Our results broaden our knowledge about macrophages in malignant microenvironments from solid tumors to leukemia.
authors: 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; and.
authors: Sha-Yan
authors: SY
authors: Chen
authors: 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; and.
authors: Xiao
authors: X
authors: Yang
authors: 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; and.
authors: Wen-Li
authors: WL
authors: Feng
authors: 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; and.
authors: Jin-Feng
authors: JF
authors: Liao
authors: 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; and.
authors: Li-Na
authors: LN
authors: Wang
authors: 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; and.
authors: Li
authors: L
authors: Feng
authors: 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; and.
authors: Yong-Min
authors: YM
authors: Lin
authors: 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; and.
authors: Qian
authors: Q
authors: Ren
authors: 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; and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China zhengggtjchn@aliyun.com.
authors: Guo-Guang
authors: http://orcid.org/0000-0002-0829-3501
authors: GG
authors: Zheng
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000276:immunology; D010641:Phenotype; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*