BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS
Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT) used in the treatment of both malignant and non-malignant diseases. Historically, t-MN has been considered to be a direct consequence of DNA damage induced in normal hematopoietic stem or progenitor cells (HS...
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| Format: | Article |
| Language: | English |
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Mattioli1885
2023-08-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
| Subjects: | |
| Online Access: | http://www.mjhid.org/index.php/mjhid/article/view/5457 |
| _version_ | 1797730941792157696 |
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| author | Maria Teresa Voso Giulia Falconi Emiliano Fabiani |
| author_facet | Maria Teresa Voso Giulia Falconi Emiliano Fabiani |
| author_sort | Maria Teresa Voso |
| collection | DOAJ |
| description |
Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT) used in the treatment of both malignant and non-malignant diseases. Historically, t-MN has been considered to be a direct consequence of DNA damage induced in normal hematopoietic stem or progenitor cells (HSPC) by CT. However, we now know that treatment-induced mutations in HSC are not the only players involved in t-MN development but additional factors may contribute to the onset of t-MN.
One of the known drivers involved in this field is the bone marrow microenvironment (BMM) and in particular bone marrow mesenchymal stem cells (BM-MSC) whose role in t-MN pathogenesis is the topic of this mini-review.
BM-MSC, physiologically, support HSC maintenance, self-renewal, and differentiation, through hematopoietic–stromal interactions and production of cytokines. In addition, BM-MSC maintain the stability of the BM immune microenvironment and reduce the damage caused to HSC by stress stimuli.
In t-MN context, chemo/radio-therapy may induce damage to the BM-MSC and likewise alter BM-MSC functions by promoting pro-inflammatory response, clonal selection and/or the production of factors that may favor malignant hematopoiesis.
Over the last decade, it has been shown that BM-MSC isolated from patients with de novo and therapy-related MN exhibit decreased proliferative and clonogenic capacity, altered morphology, increased senescence, defective osteogenic differentiation potential, impaired immune-regulatory properties, and reduced ability to support HSC growth and differentiation, as compared to normal BM-MSC.
Although the understanding of the genetic and gene expression profile associated with ex vivo-expanded t-MN-MSCs remains limited and debatable, its potential role in prognostic and therapeutic terms is acting as a flywheel of attraction of many researchers.
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| first_indexed | 2024-03-12T11:52:19Z |
| format | Article |
| id | doaj.art-44317c10838c4b2d9d072260645719d9 |
| institution | Directory Open Access Journal |
| issn | 2035-3006 |
| language | English |
| last_indexed | 2024-03-12T11:52:19Z |
| publishDate | 2023-08-01 |
| publisher | Mattioli1885 |
| record_format | Article |
| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj.art-44317c10838c4b2d9d072260645719d92023-08-31T06:08:59ZengMattioli1885Mediterranean Journal of Hematology and Infectious Diseases2035-30062023-08-0115110.4084/MJHID.2023.055BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLSMaria Teresa Voso0Giulia Falconi1Emiliano Fabiani2Università di Roma TorvergataUniversità di Roma TorvergataUniversità di Roma Torvergata; Unicamillus Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT) used in the treatment of both malignant and non-malignant diseases. Historically, t-MN has been considered to be a direct consequence of DNA damage induced in normal hematopoietic stem or progenitor cells (HSPC) by CT. However, we now know that treatment-induced mutations in HSC are not the only players involved in t-MN development but additional factors may contribute to the onset of t-MN. One of the known drivers involved in this field is the bone marrow microenvironment (BMM) and in particular bone marrow mesenchymal stem cells (BM-MSC) whose role in t-MN pathogenesis is the topic of this mini-review. BM-MSC, physiologically, support HSC maintenance, self-renewal, and differentiation, through hematopoietic–stromal interactions and production of cytokines. In addition, BM-MSC maintain the stability of the BM immune microenvironment and reduce the damage caused to HSC by stress stimuli. In t-MN context, chemo/radio-therapy may induce damage to the BM-MSC and likewise alter BM-MSC functions by promoting pro-inflammatory response, clonal selection and/or the production of factors that may favor malignant hematopoiesis. Over the last decade, it has been shown that BM-MSC isolated from patients with de novo and therapy-related MN exhibit decreased proliferative and clonogenic capacity, altered morphology, increased senescence, defective osteogenic differentiation potential, impaired immune-regulatory properties, and reduced ability to support HSC growth and differentiation, as compared to normal BM-MSC. Although the understanding of the genetic and gene expression profile associated with ex vivo-expanded t-MN-MSCs remains limited and debatable, its potential role in prognostic and therapeutic terms is acting as a flywheel of attraction of many researchers. http://www.mjhid.org/index.php/mjhid/article/view/5457t-MNBone Marrow MicroenvironmentMesenchymal Cells |
| spellingShingle | Maria Teresa Voso Giulia Falconi Emiliano Fabiani BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS Mediterranean Journal of Hematology and Infectious Diseases t-MN Bone Marrow Microenvironment Mesenchymal Cells |
| title | BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS |
| title_full | BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS |
| title_fullStr | BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS |
| title_full_unstemmed | BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS |
| title_short | BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS |
| title_sort | bone marrow microenvironment involvement in t mn focus on mesenchymal stem cells |
| topic | t-MN Bone Marrow Microenvironment Mesenchymal Cells |
| url | http://www.mjhid.org/index.php/mjhid/article/view/5457 |
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