ArticleFrontiers in immunology2019
The Complement Cascade as a Mediator of Human Malignant Hematopoietic Cell Trafficking.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.Journal of leukocyte biology · 2024Review
- External Liver-Derived Complement and Intrinsic Present in Hematopoietic Stem/Progenitor Cells Complosome Modulate Cell Metabolism and Response to Stress.Stem cell reviews and reports · 2023Review
- The role of the complosome in health and disease.Frontiers in immunology · 2023Review
- Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression.Blood advances · 2022Article
- Differential expression of plasma exosomal microRNA in severe acute pancreatitis.Frontiers in pharmacology · 2022Article
- Immunohematological and Clinical Characterization of Complement and Non-Complement Associated Warm Autoimmune Haemolytic Anemia and Risk Factors Predicting their Occurrences.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2021Article
- C3a and C5a facilitates the metastasis of myeloma cells by activating Nrf2.Cancer gene therapy · 2021Article
- Nlrp3 Inflammasome Signaling Regulates the Homing and Engraftment of Hematopoietic Stem Cells (HSPCs) by Enhancing Incorporation of CXCR4 Receptor into Membrane Lipid Rafts.Stem cell reviews and reports · 2020Article
- Acquired Aplastic Anemia as a Clonal Disorder of Hematopoietic Stem Cells.Stem cell reviews and reports · 2020Review
- How Does Complement Affect Hematological Malignancies: From Basic Mechanisms to Clinical Application.Frontiers in immunology · 2020Review
- Role of thrombomodulin expression on hematopoietic stem cells.Journal of thrombosis and haemostasis : JTH · 2020Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
The complement cascade (ComC) cleavage fragments C3a and C5a regulate the trafficking of normal, differentiated hematopoietic cells, although they do not chemoattract more primitive hematopoietic stem/progenitor cells (HSPCs). By contrast, human myeloid and lymphoid leukemia cell lines and clonogenic blasts from chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) patients respond to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. Consistent with this finding, C3a and C5a receptors are expressed by leukemic cells at the mRNA (RT-PCR) and protein (FACS) levels, and these cells respond to C3a and C5a stimulation by phosphorylation of p44/42 MAPK and AKT. However, neither of these ComC cleavage fragments have an effect on cell proliferation or survival. In parallel, we found that inducible heme oxygenase 1 (HO-1)-an anti-inflammatory enzyme, is a negative regulator of ComC-mediated trafficking of malignant cells and that stimulation of these cells by C3 or C5 cleavage fragments downregulates HO-1 expression in a p38 MAPK-dependent manner, rendering cells exposed to C3a or C5a more mobile. We propose that, while the ComC is not directly involved in the proliferation of malignant hematopoietic cells, its activation in leukemia/lymphoma patients (e.g., as a result of accompanying infections or sterile inflammation after radio-chemotherapy) enhances the motility of malignant cells and contributes to their dissemination in a p38 MAPK-HO-1 axis-dependent manner. Based on this idea, we propose that inhibition of p38 MAPK or upregulation of HO-1 by available small-molecule modulators would have a beneficial effect on ameliorating expansion and dissemination of leukemia/lymphoma cells in clinical situations in which the ComC becomes activated. Finally, since we detected expression of C3 and C5 mRNA in human leukemic cell lines, further study of the potential role of the complosome in regulating the behavior of these cells is needed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.