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 (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 withde novo and therapy-related MN exhibit decreased proliferative and clonogenic capacity, altered morphology, increased senescence, defective osteogenic differentiation potential, impaired immune-r...
Source: Mediterranean Journal of Hematology and Infectious Diseases - Category: Hematology Authors: Source Type: research