Aberrant Bone Marrow Microenvironment In Therapy Related Myeloid Neoplasm (T-Mn)

Introduction Therapy related myeloid neoplasm (t-MN) is a lethal second hematological malignancy following chemotherapy (CT) and radiotherapy (RT) for primary cancers. It accounts for 15-20% of myelodysplastic syndromes (MDS) and acute myeloid leukemia. Prognosis of t-MN is poor with no effective therapies. Although CT/RT can damage the bone marrow microenvironment, very limited studies assessed it in t-MN. Aim To compare bone marrow microenvironment milieu and mesenchymal stromal cells (MSC) from primary MDS (pMDS), t-MN and double cancers (DC, primary cancer and MDS but without a history of CT/RT for primary cancer). Methods Bone Marrow plasma cytokines/chemokines (CCK) and bone marrow MSC proliferation, senescence, morphology and differentiation potential of pMDS, t-MN and DC was compared. Results Proliferation and clonogenic potential of MSC from t-MN were significantly lower than pMDS and DC (Fig.1A). MSC from t-MN could not be maintained in culture and had higher senescence rates, assessed by β-galactosidase positive cells, compared to pMDS and DC (p Conclusions Our data demonstrate that MSC from t-MN patients have significantly altered morphology, a lower proliferation rate, and higher senescence rate compared to pMDS and DC. Osteogenic differentiation of t-MN MSC was higher at the cost of reduced adipogenic differentiation. This data suggests that RT/CT leads to long term damages to bone marrow microenvironment which may play a role in t-MN pathogenesis.