BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS MESENCHYMAL STEM CELL IN T-MN
Main Article Content
Keywords
t-MN, Bone Marrow Microenvironment, Mesenchymal Cells
Abstract
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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References
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Aug 29, 2023
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Voso, M. T., Falconi, G. and Fabiani, E. (2023) “BONE MARROW MICROENVIRONMENT INVOLVEMENT IN T-MN: FOCUS ON MESENCHYMAL STEM CELLS: MESENCHYMAL STEM CELL IN T-MN”, Mediterranean Journal of Hematology and Infectious Diseases, 15(1), p. e2023055. doi: 10.4084/MJHID.2023.055.
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Author Biography
Maria Teresa Voso, Università di Roma Torvergata
Istituto di Ematologia, Associate Professor