Year: 2022
Type: article
Abstract: Macrophages within the bone marrow (BM) microenvironment take on unexpected roles in acute myeloid leukemia (AML) as reported by Moore and colleagues in this issue of the JCI. In contrast to solid tumors, where tumor-associated macrophages frequently assume an immunosuppressive phenotype that promotes tumor progression, this study revealed that BM macrophages repressed leukemia expansion in AML through a pathway called LC3-associated phagocytosis (LAP). After phagocytosis of dead and dying leukemic cells, including the mitochondria within the leukemic blasts, mitochondrial DNA activated stimulator of IFN genes (STING), leading to inflammatory signals that enhanced phagocytosis and restrained leukemic cell expansion. These findings unveil the modulation of macrophage-mediated phagocytosis via LAP as a potential therapeutic strategy directed at the BM microenvironment in AML.
DOI: 10.1172/jci157434
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Children's Cancer Research Fund, Alex's Lemonade Stand Foundation for Childhood Cancer, Rally Foundation, MPN Research Foundation, Maryland Stem Cell Research Fund, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: High Mobility Group A1 Chromatin Regulators in Colon Carcinogenesis, HMGA Chromatin Remodeling Proteins in Tumor Progression in Myeloproliferative Neoplasms (MPN), The HMGA1 Chromatin Regulator in Hematopoietic Stem Cells with Aging, Bone Marrow Transplantation in Human Disease, Self-assembling density gradients for sickle cell diagnosis in low resource areas, Biologic and Therapeutic Consequences of Distinct Hotspot SF3B1 Mutations in MDS, G7809541869, Modeling myelodysplasia, Regional Oncology Research Center
OpenAlex ID: W4214626733