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Cell Nov 2020Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid...
Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed. Applying multimodal single-cell analyses, we elucidated a heterogeneous but spatially defined CNS-myeloid response during br-met outgrowth. We found Ccr2 BMDMs minimally influenced br-met while CNS-myeloid promoted br-met outgrowth. Additionally, br-met-associated CNS-myeloid exhibited downregulation of Cx3cr1. Cx3cr1 knockout in CNS-myeloid increased br-met incidence, leading to an enriched interferon response signature and Cxcl10 upregulation. Significantly, neutralization of Cxcl10 reduced br-met, while rCxcl10 increased br-met and recruited VISTA PD-L1 CNS-myeloid to br-met lesions. Inhibiting VISTA- and PD-L1-signaling relieved immune suppression and reduced br-met burden. Our results demonstrate that loss of Cx3cr1 in CNS-myeloid triggers a Cxcl10-mediated vicious cycle, cultivating a br-met-promoting, immune-suppressive niche.
Topics: Animals; Bone Marrow Cells; Brain Neoplasms; CX3C Chemokine Receptor 1; Central Nervous System; Chemokine CXCL10; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunosuppression Therapy; Interferons; Macrophages; Membrane Proteins; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Neutralization Tests; Phenotype; T-Lymphocytes; Transcriptome
PubMed: 33113353
DOI: 10.1016/j.cell.2020.09.064 -
Seminars in Diagnostic Pathology Nov 2020Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly... (Review)
Review
Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly depending on the nature of the diseases. The most common diseases associated with lung and pleura involvement are myeloid sarcoma/acute myeloid leukemia (AML) and extramedullary hematopoiesis (EMH). AML typically represents localized involvement by systemic acute leukemia, while EMH is frequently secondary to underlying benign hematolymphoid disorders or myeloproliferative neoplasms. This review provides an overview of the pathogenesis, clinical presentations, radiologic/imaging studies, pathologic and genetic findings, and treatment/outcomes associated with myeloid diseases in the lung and pleura.
Topics: Diagnosis, Differential; Genetic Predisposition to Disease; Hematopoiesis, Extramedullary; Humans; Leukemia, Myeloid, Acute; Lung; Myeloproliferative Disorders; Pathology, Molecular; Pleura; Sarcoma, Myeloid; Thalassemia; Treatment Outcome
PubMed: 32591154
DOI: 10.1053/j.semdp.2020.06.002 -
Haematologica Feb 2023
Review
Topics: Humans; Leukemia, Myeloid, Acute; Longitudinal Studies
PubMed: 36722401
DOI: 10.3324/haematol.2022.280803 -
International Journal of Molecular... Jun 2022Acute myeloid leukaemia (AML) is defined as a malignant disorder of the bone marrow (BM) that is characterised by the clonal expansion and differentiation arrest of...
Acute myeloid leukaemia (AML) is defined as a malignant disorder of the bone marrow (BM) that is characterised by the clonal expansion and differentiation arrest of myeloid progenitor cells [...].
Topics: Bone Marrow; Bone Marrow Cells; Humans; Leukemia, Myeloid, Acute
PubMed: 35682932
DOI: 10.3390/ijms23116251 -
The New England Journal of Medicine Aug 2020
Topics: Duodenum; Endoscopy, Digestive System; Gastrointestinal Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Sarcoma, Myeloid; Stomach
PubMed: 32846064
DOI: 10.1056/NEJMicm2001235 -
Blood Apr 2020
Topics: Adult; Female; Humans; Infant, Newborn; Leukemia, Myeloid, Acute; Placenta; Pregnancy; Pregnancy Complications, Neoplastic; Sarcoma, Myeloid
PubMed: 32298443
DOI: 10.1182/blood.2020004975 -
Haematologica Apr 2023
Topics: Humans; Leukemia, Myeloid, Acute
PubMed: 36005564
DOI: 10.3324/haematol.2022.281742 -
[Rinsho Ketsueki] the Japanese Journal... Jan 2013
Review
Topics: Genetic Predisposition to Disease; Humans; Leukemia, Myeloid, Acute; Mutation; Neoplastic Stem Cells; Prognosis; Survival Analysis
PubMed: 23391646
DOI: No ID Found -
American Journal of Hematology Jan 2016In this Review, the progress in research and therapy of acute myeloid leukemia is detailed. (Review)
Review
In this Review, the progress in research and therapy of acute myeloid leukemia is detailed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Translocation, Genetic
PubMed: 26598393
DOI: 10.1002/ajh.24246 -
Haematologica 1986
Review
Topics: Adult; Bone Marrow Transplantation; Chromosome Aberrations; Chromosomes, Human, Pair 9; Cyclophosphamide; Female; Humans; Italy; Leukemia, Myeloid; Male; Philadelphia Chromosome; Splenectomy; Whole-Body Irradiation
PubMed: 3093318
DOI: No ID Found