scholarly journals The bone marrow niche for haematopoietic stem cells

Nature ◽  
2014 ◽  
Vol 505 (7483) ◽  
pp. 327-334 ◽  
Author(s):  
Sean J. Morrison ◽  
David T. Scadden
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Niche ◽  
Haematopoietic Stem Cells

scholarly journals Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Nature ◽  
2010 ◽  
Vol 466 (7308) ◽  
pp. 829-834 ◽  
Author(s):  
Simón Méndez-Ferrer ◽  
Tatyana V. Michurina ◽  
Francesca Ferraro ◽  
Amin R. Mazloom ◽  
Ben D. MacArthur ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Niche ◽  
Haematopoietic Stem Cells

scholarly journals Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML

2019 ◽  
Vol 47 (5) ◽  
pp. 1307-1325 ◽  
Author(s):  
Caroline Busch ◽  
Helen Wheadon
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Morphogenetic Proteins ◽  
Kinase Inhibitor ◽  
Survival Rates ◽  
High Survival ◽  
Bone Marrow Niche ◽  
Matrix Deposition ◽  
Bmp Receptors ◽  
Number Of Patients

Abstract Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.

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