TY - JOUR
T1 - Mesenchymal stromal cell senescence in haematological malignancies
AU - Plakhova, Natalya
AU - Panagopoulos, Vasilios
AU - Vandyke, Kate
AU - Zannettino, Andrew C.W.
AU - Mrozik, Krzysztof M.
N1 - Funding Information:
K.V. and K.M.M. are supported by Early Career Cancer Research Fellowships from the Cancer Council SA Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health. V.P. is supported by a National Health and Medical Research Council Early Career Fellowship. This research was supported in part by a research grant from the Ray and Shirl Norman Cancer Research Trust and by grant 2013025 awarded through the 2021 Priority-driven Collaborative Cancer Research Scheme and co-funded by Cancer Australia and the Leukaemia Foundation.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/1/9
Y1 - 2023/1/9
N2 - Acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM) are age-related haematological malignancies with defined precursor states termed myelodysplastic syndrome (MDS), monoclonal B-cell lymphocytosis (MBL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. While the progression from asymptomatic precursor states to malignancy is widely considered to be mediated by the accumulation of genetic mutations in neoplastic haematopoietic cell clones, recent studies suggest that intrinsic genetic changes, alone, may be insufficient to drive the progression to overt malignancy. Notably, studies suggest that extrinsic, microenvironmental changes in the bone marrow (BM) may also promote the transition from these precursor states to active disease. There is now enhanced focus on extrinsic, age-related changes in the BM microenvironment that accompany the development of AML, CLL, and MM. One of the most prominent changes associated with ageing is the accumulation of senescent mesenchymal stromal cells within tissues and organs. In comparison with proliferating cells, senescent cells display an altered profile of secreted factors (secretome), termed the senescence-associated-secretory phenotype (SASP), comprising proteases, inflammatory cytokines, and growth factors that may render the local microenvironment favourable for cancer growth. It is well established that BM mesenchymal stromal cells (BM-MSCs) are key regulators of haematopoietic stem cell maintenance and fate determination. Moreover, there is emerging evidence that BM-MSC senescence may contribute to age-related haematopoietic decline and cancer development. This review explores the association between BM-MSC senescence and the development of haematological malignancies, and the functional role of senescent BM-MSCs in the development of these cancers.
AB - Acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM) are age-related haematological malignancies with defined precursor states termed myelodysplastic syndrome (MDS), monoclonal B-cell lymphocytosis (MBL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. While the progression from asymptomatic precursor states to malignancy is widely considered to be mediated by the accumulation of genetic mutations in neoplastic haematopoietic cell clones, recent studies suggest that intrinsic genetic changes, alone, may be insufficient to drive the progression to overt malignancy. Notably, studies suggest that extrinsic, microenvironmental changes in the bone marrow (BM) may also promote the transition from these precursor states to active disease. There is now enhanced focus on extrinsic, age-related changes in the BM microenvironment that accompany the development of AML, CLL, and MM. One of the most prominent changes associated with ageing is the accumulation of senescent mesenchymal stromal cells within tissues and organs. In comparison with proliferating cells, senescent cells display an altered profile of secreted factors (secretome), termed the senescence-associated-secretory phenotype (SASP), comprising proteases, inflammatory cytokines, and growth factors that may render the local microenvironment favourable for cancer growth. It is well established that BM mesenchymal stromal cells (BM-MSCs) are key regulators of haematopoietic stem cell maintenance and fate determination. Moreover, there is emerging evidence that BM-MSC senescence may contribute to age-related haematopoietic decline and cancer development. This review explores the association between BM-MSC senescence and the development of haematological malignancies, and the functional role of senescent BM-MSCs in the development of these cancers.
KW - Haematological malignancy
KW - Leukaemia
KW - Mesenchymal stromal cells
KW - Multiple myeloma
KW - Senescence
UR - http://www.scopus.com/inward/record.url?scp=85145886689&partnerID=8YFLogxK
U2 - 10.1007/s10555-022-10069-9
DO - 10.1007/s10555-022-10069-9
M3 - Review article
AN - SCOPUS:85145886689
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
SN - 0167-7659
ER -