Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells
Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environment...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fonc.2017.00265/full |
| _version_ | 1818193856065175552 |
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| author | Shayda Hemmati Shayda Hemmati Tamanna Haque Tamanna Haque Tamanna Haque Kira Gritsman Kira Gritsman Kira Gritsman |
| author_facet | Shayda Hemmati Shayda Hemmati Tamanna Haque Tamanna Haque Tamanna Haque Kira Gritsman Kira Gritsman Kira Gritsman |
| author_sort | Shayda Hemmati |
| collection | DOAJ |
| description | Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to deactivate this response and return to steady state. Prolonged or excessive exposure to inflammatory cytokines, such as in prolonged infection or in chronic rheumatologic conditions, can lead to continued HSC cycling and eventual HSC loss. This promotes bone marrow failure, and can precipitate preleukemic states or leukemia through the acquisition of genetic and epigenetic changes in HSCs. This can occur through the initiation of clonal hematopoiesis, followed by the emergence preleukemic stem cells (pre-LSCs). In this review, we describe the roles of multiple inflammatory signaling pathways in the generation of pre-LSCs and in progression to myelodysplastic syndrome (MDS), myeloproliferative neoplasms, and acute myeloid leukemia (AML). In AML, activation of some inflammatory signaling pathways can promote the cycling and differentiation of LSCs, and this can be exploited therapeutically. We also discuss the therapeutic potential of modulating inflammatory signaling for the treatment of myeloid malignancies. |
| first_indexed | 2024-12-12T00:53:02Z |
| format | Article |
| id | doaj.art-46ef0b59ffe841ac8c987c66ab912e5a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T00:53:02Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-46ef0b59ffe841ac8c987c66ab912e5a2022-12-22T00:43:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2017-11-01710.3389/fonc.2017.00265299732Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem CellsShayda Hemmati0Shayda Hemmati1Tamanna Haque2Tamanna Haque3Tamanna Haque4Kira Gritsman5Kira Gritsman6Kira Gritsman7Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Oncology, Montefiore Medical Center, Bronx, NY, United StatesDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Oncology, Montefiore Medical Center, Bronx, NY, United StatesHematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to deactivate this response and return to steady state. Prolonged or excessive exposure to inflammatory cytokines, such as in prolonged infection or in chronic rheumatologic conditions, can lead to continued HSC cycling and eventual HSC loss. This promotes bone marrow failure, and can precipitate preleukemic states or leukemia through the acquisition of genetic and epigenetic changes in HSCs. This can occur through the initiation of clonal hematopoiesis, followed by the emergence preleukemic stem cells (pre-LSCs). In this review, we describe the roles of multiple inflammatory signaling pathways in the generation of pre-LSCs and in progression to myelodysplastic syndrome (MDS), myeloproliferative neoplasms, and acute myeloid leukemia (AML). In AML, activation of some inflammatory signaling pathways can promote the cycling and differentiation of LSCs, and this can be exploited therapeutically. We also discuss the therapeutic potential of modulating inflammatory signaling for the treatment of myeloid malignancies.http://journal.frontiersin.org/article/10.3389/fonc.2017.00265/fullinflammatorypreleukemicleukemic stem celltoll-like receptortumor necrosis factorinterferon |
| spellingShingle | Shayda Hemmati Shayda Hemmati Tamanna Haque Tamanna Haque Tamanna Haque Kira Gritsman Kira Gritsman Kira Gritsman Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells Frontiers in Oncology inflammatory preleukemic leukemic stem cell toll-like receptor tumor necrosis factor interferon |
| title | Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells |
| title_full | Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells |
| title_fullStr | Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells |
| title_full_unstemmed | Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells |
| title_short | Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells |
| title_sort | inflammatory signaling pathways in preleukemic and leukemic stem cells |
| topic | inflammatory preleukemic leukemic stem cell toll-like receptor tumor necrosis factor interferon |
| url | http://journal.frontiersin.org/article/10.3389/fonc.2017.00265/full |
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