The Bone Marrow Microenvironment in Health and Myeloid Malignancy

Galán-Díez, Marta; Cuesta-Domínguez, Álvaro; Kousteni, Stavroula

doi:10.1101/cshperspect.a031328

Cited by 40 publications

(35 citation statements)

References 137 publications

(174 reference statements)

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“…Despite a good understanding of the role of macrophages in solid tumours, little is known about this in haematopoietic malignancies. Compared with solid tumours, leukaemia and leukaemia‐associated monocyte‐derived cells (LAMs) have different clinical features because of their special microenvironment 12 . Leukaemic stem cells can remodel the bone marrow (BM) niche into a self‐reinforcing leukaemic niche 12‐14 .…”

Section: Introductionmentioning

confidence: 99%

“…Compared with solid tumours, leukaemia and leukaemia‐associated monocyte‐derived cells (LAMs) have different clinical features because of their special microenvironment 12 . Leukaemic stem cells can remodel the bone marrow (BM) niche into a self‐reinforcing leukaemic niche 12‐14 . This might enhance the leukaemic stem cells’ quiescence, leading to tumour progression and chemotherapy resistance.…”

Section: Introductionmentioning

confidence: 99%

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CSF‐1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression

Wen

et al. 2020

J Cellular Molecular Medi

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Research in the last few years has revealed that leukaemic cells can remodel the bone marrow niche into a permissive environment favouring leukaemic stem cell expansion. Tumour‐associated macrophages (TAMs) are prominent components of the tumour microenvironment and play an important role in the onset and progression of solid tumours. However, little is known about their role in the development of acute lymphoblastic leukaemia (ALL). Using a unique mouse model of T‐ALL induced by injection of EL4 T‐cell lymphoma cells to syngeneic C57BL/6 mice, we report herein that ALL leads to the invasion of leukaemia‐associated monocyte‐derived cells (LAMs) into the bone marrow and spleen of T‐ALL mice. Furthermore, we found that leukaemia cells could polarize bone marrow–derived macrophages (BMDMs) into LAMs. In turn, LAMs were able to protect leukaemia cells from drug‐induced apoptosis in vitro. Therapies targeted against the TAMs by inhibiting colony stimulating factor‐1 receptor (CSF‐1R) have emerged as a promising approach for cancer treatment. In this study, we demonstrate that CSF‐1R inhibition inhibits the viability of BMDMs, blocks LAMs polarization and reduces the abundance of LAMs in T‐ALL mice. In vivo, combination treatment of CSF‐1R inhibitor and vincristine (VCR) dramatically increased the survival of T‐ALL mice and delayed leukaemia progression compared with VCR monotherapy. Finally, these data reinforce the role of microenvironments in leukaemia and suggest that macrophages are a potential target for the development of novel therapeutic strategies in T‐ALL.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CSF‐1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression

Wen

et al. 2020

J Cellular Molecular Medi

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“…The ROS low HSCs found in sinusoidal areas reside near megakaryocytes, which in the BM niche promote HSC quiescence through secretion of transforming growth factor beta (TGF-β), thrombopoietin (TPO) or platelet factor 4 (PF-4). sECs also express higher levels of E-selectin (adhesion molecule that supports HSC activation) than aECs [ 32 , 33 ]. Sympathetic nerve fibers innervate BM perivascular areas and contribute to their functional differentiation.…”

Section: Bone Marrow Microenvironment Home Of Hematological Maligmentioning

confidence: 99%

“…Non myelinating Schwann cells (nmSCs) in sBMN regulate migration of HSCs by direct contact [ 31 ], while Nest + nmSCs maintain hibernating HSCs in aBMN [ 34 ]. nmSCs associated with sympathetic nerve fibers can promote HSC quiescence by activating latent TFG-β in EBMN and CMBN [ 33 ]. Sympathetic nerves release soluble mediators such as catecholamines from terminals.…”

Section: Bone Marrow Microenvironment Home Of Hematological Maligmentioning

confidence: 99%

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

Clara-Trujillo

Ferrer

Ribelles

2020

IJMS

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In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.

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“…Bone is also an important reservoir for several minerals including calcium, phosphate, and magnesium (see Murshed 2017;Whyte 2017). Finally, bone cells are involved in the maintenance of the hematopoietic stem cell niche and, hence, in the production of lymphocytes, erythrocytes, and platelets (see Frenette 2017;Galán-Díez et al 2017;Roodman 2017). All these functions of bones are regulated by specific hormonal and neuronal pathways acting on bone cells, which have been extensively covered in the literature.…”

mentioning

confidence: 99%

Regulation of Energy Metabolism by Bone-Derived Hormones

Mera

Ferron

Mosialou

2017

Cold Spring Harb Perspect Med

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Like many other organs, bone can act as an endocrine organ through the secretion of bone-specific hormones or "osteokines." At least two osteokines are implicated in the control of glucose and energy metabolism: osteocalcin (OCN) and lipocalin-2 (LCN2). OCN stimulates the production and secretion of insulin by the pancreatic β-cells, but also favors adaptation to exercise by stimulating glucose and fatty acid (FA) utilization by the muscle. Both of these OCN functions are mediated by the G-protein-coupled receptor GPRC6A. In contrast, LCN2 influences energy metabolism by activating appetite-suppressing signaling in the brain. This action of LCN2 occurs through its binding to the melanocortin 4 receptor (MC4R) in the paraventricular nucleus of the hypothalamus (PVN) and ventromedial neurons of the hypothalamus.

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The Bone Marrow Microenvironment in Health and Myeloid Malignancy

Cited by 40 publications

References 137 publications

CSF‐1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression

CSF‐1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

Regulation of Energy Metabolism by Bone-Derived Hormones

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