Role of bone marrow adipocytes in leukemia and chemotherapy challenges

Samimi, Azin; Ghanavat, Majid; Shahrabi, Saeid; Azizidoost, Shirin; Saki, Najmaldin

doi:10.1007/s00018-019-03031-6

Cited by 18 publications

(7 citation statements)

References 92 publications

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“…When tumor cells migrating from other tissues are located in the BMM, adipocytes will be recruited and deliver lipids to tumor cells via the CD36 receptor ( 162 ). In addition, these adipocytes secrete a set of inflammatory adipokines, such as leptin, tumor necrosis factor-alpha (TNF-α), and IL-6, as well as an anti-inflammatory adipokine, called adiponectin, to modulate the immunological microenvironment ( 163 ). Furthermore, adipocytes have been found to induce the differentiation of bone marrow precursors into adipose tissue macrophage-like cells via releasing exosome-sized, lipid-filled vesicles ( 164 ).…”

Section: Impact Of Metabolic Regulation On Anti-leukemia Immune Responsesmentioning

confidence: 99%

The Importance of Cellular Metabolic Pathways in Pathogenesis and Selective Treatments of Hematological Malignancies

et al. 2021

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Despite recent advancements in the treatment of hematologic malignancies and the emergence of newer and more sophisticated therapeutic approaches such as immunotherapy, long-term overall survival remains unsatisfactory. Metabolic alteration, as an important hallmark of cancer cells, not only contributes to the malignant transformation of cells, but also promotes tumor progression and metastasis. As an immune-escape mechanism, the metabolic adaptation of the bone marrow microenvironment and leukemic cells is a major player in the suppression of anti-leukemia immune responses. Therefore, metabolic rewiring in leukemia would provide promising opportunities for newer therapeutic interventions. Several therapeutic agents which affect essential bioenergetic pathways in cancer cells including glycolysis, β-oxidation of fatty acids and Krebs cycle, or anabolic pathways such as lipid biosynthesis and pentose phosphate pathway, are being tested in various types of cancers. So far, numerous preclinical or clinical trial studies using such metabolic agents alone or in combination with other remedies such as immunotherapy are in progress and have demonstrated promising outcomes. In this review, we aim to argue the importance of metabolic alterations and bioenergetic pathways in different types of leukemia and their vital roles in disease development. Designing treatments based on targeting leukemic cells vulnerabilities, particularly in nonresponsive leukemia patients, should be warranted.

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Section: Impact Of Metabolic Regulation On Anti-leukemia Immune Responsesmentioning

confidence: 99%

The Importance of Cellular Metabolic Pathways in Pathogenesis and Selective Treatments of Hematological Malignancies

et al. 2021

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“…Furthermore, adipocytes are also known to contribute to leukaemic chemoresistance by metabolising and inactivating drugs in the BM [39]. Thus, the concept of targeting adipocytes in the leukaemic BMM remains an attractive proposition due to their influence as a protective niche for malignant cells and has been extensively reviewed [40,41].…”

Section: Adipocytic Niche In Leukaemiamentioning

confidence: 99%

Therapeutic Targeting of the Leukaemia Microenvironment

Kuek

Hughes

Kotecha

et al. 2021

IJMS

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In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia.

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“…Additional mechanisms of BMA involvement in hematological malignancy progression may include secretion of mediators, such as TNF-α, IL-6, leptin and adiponectin [148]. Leptin activates its receptor on malignant cells from a range of myeloid and lymphoid neoplasms leading to stimulation of cell proliferation and cytokine secretion, and protection from apoptosis, through JAK-STAT, MAPK/ERK1/2, or PI3K signaling pathways [149].…”

Section: Role Of Bma In Malignant Hematopoiesismentioning

confidence: 99%

Bone Marrow Adipocytes: The Enigmatic Components of the Hematopoietic Stem Cell Niche

Cuminetti

Arranz

2019

JCM

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Bone marrow adipocytes (BMA) exert pleiotropic roles beyond mere lipid storage and filling of bone marrow (BM) empty spaces, and we are only now beginning to understand their regulatory traits and versatility. BMA arise from the differentiation of BM mesenchymal stromal cells, but they seem to be a heterogeneous population with distinct metabolisms, lipid compositions, secretory properties and functional responses, depending on their location in the BM. BMA also show remarkable differences among species and between genders, they progressively replace the hematopoietic BM throughout aging, and play roles in a range of pathological conditions such as obesity, diabetes and anorexia. They are a crucial component of the BM microenvironment that regulates hematopoiesis, through mechanisms largely unknown. Previously considered as negative regulators of hematopoietic stem cell function, recent data demonstrate their positive support for hematopoietic stem cells depending on the experimental approach. Here, we further discuss current knowledge on the role of BMA in hematological malignancies. Early hints suggest that BMA may provide a suitable metabolic niche for the malignant growth of leukemic stem cells, and protect them from chemotherapy. Future in vivo functional work and improved isolation methods will enable determining the true essence of this elusive BM hematopoietic stem cell niche component, and confirm their roles in a range of diseases. This promising field may open new pathways for efficient therapeutic strategies to restore hematopoiesis, targeting BMA.

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Role of bone marrow adipocytes in leukemia and chemotherapy challenges

Cited by 18 publications

References 92 publications

The Importance of Cellular Metabolic Pathways in Pathogenesis and Selective Treatments of Hematological Malignancies

The Importance of Cellular Metabolic Pathways in Pathogenesis and Selective Treatments of Hematological Malignancies

Therapeutic Targeting of the Leukaemia Microenvironment

Bone Marrow Adipocytes: The Enigmatic Components of the Hematopoietic Stem Cell Niche

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