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Pediatric Hematology and Oncology 2017Signaling between leukemia cells and nonhematopoietic cells in the bone marrow microenvironment contributes to leukemia cell growth and survival. This complicated... (Review)
Review
Signaling between leukemia cells and nonhematopoietic cells in the bone marrow microenvironment contributes to leukemia cell growth and survival. This complicated extrinsic mechanism of chemotherapy resistance relies on a number of pathways and factors, some of which have yet to be determined. Research on cell-cell crosstalk the bone marrow microenvironment in acute leukemia was presented at the 2016 annual Therapeutic Advances in Childhood Leukemia (TACL) investigator meeting. This review summarizes the mini-symposium proceedings and focuses on chemokine signaling via the cell surface receptor CXCR4, adhesion molecule signaling via integrin α4, and crosstalk between leukemia cells and the bone marrow microenvironment that is mediated through extracellular vesicles.
Topics: Animals; Bone Marrow; Chemokines; Hematologic Neoplasms; Humans; Integrins; Neoplasm Proteins; Signal Transduction; Tumor Microenvironment
PubMed: 29211600
DOI: 10.1080/08880018.2017.1395938 -
Diagnostic and Interventional Radiology... 2013Magnetic resonance imaging (MRI) is essential for evaluating bone marrow. Bone marrow undergoes constant modification and its appearance on MRI changes in response.... (Review)
Review
Magnetic resonance imaging (MRI) is essential for evaluating bone marrow. Bone marrow undergoes constant modification and its appearance on MRI changes in response. Knowledge of the types of changes and their origins is essential for analysis of MRI findings of bone marrow infiltration with hematological malignancies. This pictorial review describes the MRI pulse sequences used for imaging of bone marrow, and illustrates bone marrow changes due hematological malignancies, including changes following treatment.
Topics: Bone Marrow; Hematologic Neoplasms; Humans; Magnetic Resonance Imaging
PubMed: 23748035
DOI: 10.5152/dir.2013.067 -
Hematology. American Society of... Dec 2017Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The... (Review)
Review
Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The type and severity of hematopoietic dysfunction in MDS are highly variable, and the kinetics of disease progression are difficult to predict. Genomic studies have shown that MDS is typically driven by a multistep somatic genetic process affecting a core set of genes. By definition, recurrent MDS driver mutations all drive clonal dominance, although they can have stereotyped positions in the clonal hierarchy or patterns of comutation association and exclusivity. Furthermore, environmental context, such as exposures to cytotoxic chemotherapy or the presence of germ-line predisposition, can influence disease pathogenesis and clinical outcomes. This review will address how an enhanced understanding of MDS genetics may enable refinement of current diagnostic schema, improve understanding of the pathogenesis of therapy-related MDS, and identify germ-line predispositions to development of MDS that are more common than recognized by standard clinical evaluation.
Topics: Bone Marrow; Hematopoiesis; Humans; Mutation; Myelodysplastic Syndromes
PubMed: 29222292
DOI: 10.1182/asheducation-2017.1.447 -
Environmental Health Perspectives Jun 1981Hematopoietic system toxicity is a major limiting factor in the use of aggressive combined modality therapy in the treatment of malignant disease. In this review, the... (Review)
Review
Hematopoietic system toxicity is a major limiting factor in the use of aggressive combined modality therapy in the treatment of malignant disease. In this review, the known drug-x-ray interactions using tissue culture systems are extended to the bone marrow compartment. Two hypotheses prevail for late bone marrow failure: (1) stromal damage to the vasculature with subsequent fibrosis and (2) irreversible stem cell depletion in the irradiated site. Clinical extensions of the experimental data for bone marrow kinetics in the animal model have not proven successful to date. The future strategies for therapy of malignancies in which both radiation and chemotherapy are employed may require dose modification or treatment planning to limit bone marrow toxicity.
Topics: Animals; Bone Marrow; Bone Marrow Diseases; Humans; Physical Phenomena; Physics; Radiation Injuries, Experimental
PubMed: 7016523
DOI: 10.1289/ehp.813959 -
Experimental Hematology Jan 2022Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect... (Review)
Review
Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect malignant pathogenesis, and the dysregulated immune environment which causes the resistance to treatment. On activation, various types of protein tyrosine kinases in the cytoplasm mediate the cascade, leading to the transcription of target genes in the nucleus. Adaptor molecules are commonly defined as proteins that lack enzymatic activity, DNA-binding or receptor functions and possess protein-protein or protein-lipid interaction domains. By binding to specific domains of signaling molecules, adaptor proteins adjust the signaling responses after the ligation of receptors of soluble factors, including cytokines, chemokines, and growth factors, as well as pattern recognition receptors such as toll-like receptors. The signal-transducing adaptor protein (STAP) family regulates various intracellular signaling pathways. These proteins have a pleckstrin homology domain in the N-terminal region and an SRC-homology 2-like domain in the central region, representing typical binding structures as adapter proteins. Following the elucidation of the effects of STAPs on terminally differentiated immune cells, such as macrophages, T cells, mast cells, and basophils, recent findings have indicated the critical roles of STAP-2 in B-cell progenitor cells in marrow under hematopoietic stress and STAP-1 and -2 in BCR-ABL-transduced leukemogenesis. In this review, we focus on the role of STAPs in the bone marrow.
Topics: Adaptor Proteins, Signal Transducing; Animals; Bone Marrow; Hematologic Neoplasms; Hematopoiesis; Humans; Phosphoproteins; Signal Transduction
PubMed: 34780812
DOI: 10.1016/j.exphem.2021.11.002 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2013Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by widespread involvement of the bone marrow (BM). The BM microenvironment serves as... (Review)
Review
Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by widespread involvement of the bone marrow (BM). The BM microenvironment serves as not only a site for disease involvement, but it also appears that the interaction of WM cells with the BM is essential for the pathogenesis of WM. The BM microenvironment consists of the cellular and noncellular compartments. The BM has been shown to regulate cell proliferation, cell cycle, and drug resistance as well as cell dissemination and cell trafficking of WM cells. A better understanding of the role of the BM microenvironment in the pathogenesis of WM can help guide better therapeutic strategies that can target the tumor clone and also regulate the BM microenvironment.
Topics: Bone Marrow; Bone Marrow Cells; Cellular Microenvironment; Humans; Waldenstrom Macroglobulinemia
PubMed: 23490994
DOI: 10.1016/j.clml.2013.02.006 -
Scientific Reports Apr 2023This retrospective cross-sectional study investigated the association between bone marrow lesions (BMLs) and bone mineral density (BMD) in the proximal tibia of...
This retrospective cross-sectional study investigated the association between bone marrow lesions (BMLs) and bone mineral density (BMD) in the proximal tibia of end-stage osteoarthritic knees from a large patient sample. Overall, 1308 end-stage osteoarthritic knees were enrolled before total knee arthroplasty. The preoperative range of motion was recorded. Bone mineral density in the medial tibial plateau (MTP), lateral tibial plateau (LTP), and metaphysis were measured using dual-energy X-ray absorptiometry. The MTP/LTP, MTP/metaphysis, and LTP/metaphysis ratios were calculated. BMLs were scored using a whole-organ magnetic resonance imaging scoring system. The relationship between BMD and BML scores was investigated using linear regression analysis. The highest BMD was 0.787 ± 0.176 g/cm at the MTP, followed by 0.676 ± 0.180 g/cm and 0.572 ± 0.145 g/cm at the metaphysis and LTP, respectively. The prevalence of BMLs was 90.4% and 24.2% in the MTP and LTP, respectively. In women, higher BML scores at the MTP were positively correlated with the BMD of the MTP (p < 0.001, r = 0.278), MTP/LTP (p < 0.001, r = 0.267), and MTP/metaphysis ratios (p < 0.001, r = 0.243). Regression analysis showed that higher BML scores in the MTP were correlated with higher BMD in the MTP (p < 0.001) and lower BMD in the LTP (p < 0.001). High BML scores in the MTP were positively associated with high BMD in the MTP, which also induced the medial to lateral imbalance of BMD in the proximal tibia.
Topics: Humans; Female; Bone Density; Tibia; Bone Marrow; Osteoarthritis, Knee; Retrospective Studies; Cross-Sectional Studies; Knee Joint; Bone Diseases
PubMed: 37085519
DOI: 10.1038/s41598-023-33251-7 -
Current Oncology (Toronto, Ont.) Dec 2022Multiple myeloma (MM) is a complex disease driven by numerous genetic and epigenetic alterations that are acquired over time. Despite recent progress in the... (Review)
Review
Multiple myeloma (MM) is a complex disease driven by numerous genetic and epigenetic alterations that are acquired over time. Despite recent progress in the understanding of MM pathobiology and the availability of innovative drugs, which have pronounced clinical outcome, this malignancy eventually progresses to a drug-resistant lethal stage and, thus, novel therapeutic drugs/models always play an important role in effective management of MM. Modulation of tumor microenvironment is one of the hallmarks of cancer biology, including MM, which affects the myeloma genomic architecture and disease progression subtly through chromatin modifications. The bone marrow niche has a prime role in progression, survival, and drug resistance of multiple myeloma cells. Therefore, it is important to develop means for targeting the ecosystem between multiple myeloma bone marrow microenvironment and chromatin remodeling. Extensive gene expression profile analysis has indeed provided the framework for new risk stratification of MM patients and identifying novel molecular targets and therapeutics. However, key tumor microenvironment factors/immune cells and their interactions with chromatin remodeling complex proteins that drive MM cell growth and progression remain grossly undefined.
Topics: Humans; Multiple Myeloma; Tumor Microenvironment; Chromatin Assembly and Disassembly; Ecosystem; Bone Marrow
PubMed: 36547163
DOI: 10.3390/curroncol29120749 -
Haematologica Nov 2015Our understanding of the biology of the normal hematopoietic stem cell niche has increased steadily due to improved murine models and sophisticated imaging tools. Less... (Review)
Review
Our understanding of the biology of the normal hematopoietic stem cell niche has increased steadily due to improved murine models and sophisticated imaging tools. Less well understood, but of growing interest, is the interaction between cells in the bone marrow during the initiation, maintenance and treatment of hematologic neoplasms. This review summarizes the emerging concepts of the normal and leukemic hematopoietic bone marrow niche. Furthermore, it reviews current models of how the microenvironment of the bone marrow may contribute to or be modified by leukemogenesis. Finally, it provides the rationale for a "two-pronged" approach, directly targeting cancer cells themselves while also targeting the bone microenvironment to make it inhospitable to malignant cells and, ultimately, eradicating cancer stem-like cells.
Topics: Animals; Bone Marrow; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Stem Cell Niche; Tumor Microenvironment
PubMed: 26521296
DOI: 10.3324/haematol.2014.113852 -
Molecules (Basel, Switzerland) Apr 2022In this study, the influence of the living conditions of red deer (Cervus elaphus) fawns (wild vs. farmed) and effect of the category of free-living animals (fawns vs....
In this study, the influence of the living conditions of red deer (Cervus elaphus) fawns (wild vs. farmed) and effect of the category of free-living animals (fawns vs. does) on the fatty acid (FA) profile of the leg bone marrow was assessed. The composition of FAs in the deer bone marrow was determined by the gas chromatography method. In all groups, oleic acid (18:1 c9) was the most abundant in deer bone marrow and comprised of approximately 37% of total FAs. The bone marrow of young wild deer was characterized by a significantly (p < 0.001) higher fat content and saturated FAs proportion, while farmed fawns contained more moisture (p < 0.005) and fat-free dry matter (p < 0.001), as well as more monounsaturated FAs cis branched-chain FAs and monounsaturated FAs trans (p < 0.001). Although no significant (p > 0.05) differences were found between fawns, in terms of partial sums of PUFA, a significantly (p < 0.001) higher level of the sum of n-3 and n-6 FAs and more favorable n-6/n-3 ratio in the bone marrow of wild fawns were determined. In general, the legs of wild fawns were better prepared for wintering than farmed ones. In turn, comparing the category-related FAs composition in the bone marrow of free-living animals, a more favorable profile was observed in the adult (does) than in the young (fawns) animals, as the bone marrow of the wild does was characterized by significantly (p < 0.001) lower percentages of saturated FAs and a higher percentage of monounsaturated FAs cis.
Topics: Animals; Animals, Wild; Bone Marrow; Deer; Ecosystem; Fatty Acids
PubMed: 35458708
DOI: 10.3390/molecules27082511