This review focuses on providing physicians with insights into the complex relationship between bone marrow adipose tissue (BMAT) and bone health, in the context of weight loss through caloric restriction or metabolic and bariatric surgery (MBS), in people living with obesity (PwO). We summarize the complex relationship between BMAT and bone health, provide an overview of noninvasive imaging techniques to quantify human BMAT, and discuss clinical studies measuring BMAT in PwO before and after weight loss. The relationship between BMAT and bone is subject to variations based on factors such as age, sex, menopausal status, skeletal sites, nutritional status, and metabolic conditions. The Bone Marrow Adiposity Society (BMAS) recommends standardizing imaging protocols to increase comparability across studies and sites, they have identified both water-fat imaging (WFI) and spectroscopy (1H-MRS) as accepted standards for in vivo quantification of BMAT. Clinical studies measuring BMAT in PwO are limited and have shown contradictory results. However, BMAT tends to be higher in patients with the highest visceral adiposity, and inverse associations between BMAT and bone mineral density (BMD) have been consistently found in PwO. Furthermore, BMAT levels tend to decrease after caloric restriction-induced weight loss. Although weight loss was associated with overall fat loss, a reduction in BMAT did not always follow the changes in fat volume in other tissues. The effects of MBS on BMAT are not consistent among the studies, which is at least partly related to the differences in the study population, skeletal site, and duration of the follow-up. Overall, gastric bypass appears to decrease BMAT, particularly in patients with diabetes and postmenopausal women, whereas sleeve gastrectomy appears to increase BMAT. More research is necessary to evaluate changes in BMAT and its connection to bone metabolism, either in PwO or in cases of weight loss through caloric restriction or MBS, to better understand the role of BMAT in this context and determine the local or systemic factors involved.

• MeSH
• hmotnostní úbytek MeSH
• kostní denzita MeSH
• kostní dřeň * metabolismus   MeSH
• lidé MeSH
• obezita metabolismus   MeSH
• tuková tkáň * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

• MeSH
• adipozita MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň * metabolismus   MeSH
• kyseliny mastné omega-3 * farmakologie   metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• obezita komplikace   prevence a kontrola   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL.

• MeSH
• dospělí MeSH
• kostní dřeň metabolismus   patologie   MeSH
• kožní nemoci patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastocytóza diagnóza   epidemiologie   metabolismus   MeSH
• mastocyty metabolismus   patologie   MeSH
• míra přežití MeSH
• následné studie MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• systémová mastocytóza diagnóza   epidemiologie   metabolismus   MeSH
• tryptasy metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVES: Our aim was to correlate serum levels of selected markers of bone metabolism and bone marrow microenvironment to cytogenetic changes in patients with multiple myeloma (MM). METHODS: We assed cytogenetic changes in 308 patients and correlated them with the following levels of bone marrow metabolism: thymidine kinase (TK), β2-microglobulin (b-2-m), Dickkopf-1 protein (DKK-1), C-terminal telopeptide collagen-I (ICTP), N-terminal propeptide of type I procollagen (PINP), receptor for interleukin 6 (rIL-6), vascular cell adhesive molecule-1 (VCAM), soluble intercellular adhesion molecule-1, osteoprotegerin (OPG), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), syndecan-1 (SYN-1) and Fas antigen. RESULT: Individuals with delRB1 had lower levels of OPG (M = 7.39 vs. 5.46 pmol/L, p = .025) and VEGF (M = 304 vs. 196 pg/ml; p = .036). t(14;16) was associated with higher β2m levels (M = 7.59 vs. 4.13 mg/L; p = .022) and lower DKK-1 levels (M = 4465 ng/L vs. 12,593). The presence of 1q21 gain was associated with higher levels of TK (M = 100.0 vs. 11.0 IU/L, p = .026) and lower levels of PINP (M = 49.3 vs. 67.4 mg/L, p = .030). CONCLUSIONS: Our analysis has shown, some cytogenetic changes, especially delRB1, t(14;16) and 1q21gain, which affect the components of the cytokine network in multiple myeloma.

• MeSH
• biologické markery MeSH
• cytogenetické vyšetření MeSH
• kostní dřeň metabolismus   MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   genetika   MeSH
• nádorové mikroprostředí MeSH
• vaskulární endoteliální růstový faktor A MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• adipozita MeSH
• C-reaktivní protein fyziologie   MeSH
• diabetes mellitus 2. typu * komplikace   metabolismus   MeSH
• diabetické angiopatie metabolismus   MeSH
• interleukin-1 fyziologie   MeSH
• interleukin-6 fyziologie   MeSH
• kostní dřeň metabolismus   MeSH
• kostní matrix * metabolismus   patofyziologie   MeSH
• lidé MeSH
• obezita komplikace   metabolismus   MeSH
• osteocyty fyziologie   metabolismus   patologie   MeSH
• osteoklasty fyziologie   patologie   MeSH
• osteoporóza etiologie   komplikace   patofyziologie   MeSH
• produkty pokročilé glykace metabolismus   škodlivé účinky   MeSH
• reaktivní formy kyslíku MeSH
• TNF-alfa fyziologie   MeSH
• tuková tkáň imunologie   metabolismus   MeSH
• Check Tag
• lidé MeSH

Extramedullary disease (EMM) represents a rare, aggressive and mostly resistant phenotype of multiple myeloma (MM). EMM is frequently associated with high-risk cytogenetics, but their complex genomic architecture is largely unexplored. We used whole-genome optical mapping (Saphyr, Bionano Genomics) to analyse the genomic architecture of CD138+ cells isolated from bone-marrow aspirates from an unselected cohort of newly diagnosed patients with EMM (n = 4) and intramedullary MM (n = 7). Large intrachromosomal rearrangements (> 5 Mbp) within chromosome 1 were detected in all EMM samples. These rearrangements, predominantly deletions with/without inversions, encompassed hundreds of genes and led to changes in the gene copy number on large regions of chromosome 1. Compared with intramedullary MM, EMM was characterised by more deletions (size range of 500 bp-50 kbp) and fewer interchromosomal translocations, and two EMM samples had copy number loss in the 17p13 region. Widespread genomic heterogeneity and novel aberrations in the high-risk IGH/IGK/IGL, 8q24 and 13q14 regions were detected in individual patients but were not specific to EMM/MM. Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.

• MeSH
• buňky kostní dřeně patologie   MeSH
• celogenomová asociační studie metody   MeSH
• chromozomální aberace * MeSH
• cytogenetické vyšetření metody   MeSH
• kohortové studie MeSH
• kostní dřeň diagnostické zobrazování   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 1 * genetika   MeSH
• mnohočetný myelom genetika   patologie   MeSH
• pilotní projekty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Myelodysplastic syndromes (MDS) are preleukemic disorders characterized by clonal growth of mutant hematopoietic stem and progenitor cells. MDS are associated with proinflammatory signaling, dysregulated immune response, and cell death in the bone marrow (BM). Aging, autoinflammation and autoimmunity are crucial features of disease progression, concordant with promoting growth of malignant clones and accumulation of mutations. Suprabasin (SBSN), a recently proposed proto-oncogene of unknown function, physiologically expressed in stratified epithelia, is associated with poor prognosis of several human malignancies. Here, we showed that SBSN is expressed in the BM by myeloid cell subpopulations, including myeloid-derived suppressor cells, and is secreted into BM plasma and peripheral blood of MDS patients. The highest expression of SBSN was present in a patient group with poor prognosis. SBSN levels in the BM correlated positively with blast percentage and negatively with CCL2 chemokine levels and lymphocyte count. In vitro treatment of leukemic cells with interferon-gamma and demethylating agent 5-azacytidine (5-AC) induced SBSN expression. This indicated that aberrant cytokine levels in the BM and epigenetic landscape modifications in MDS patients may underlie ectopic expression of SBSN. Our findings suggest SBSN as a candidate biomarker of high-risk MDS with a possible role in disease progression and therapy resistance.

• MeSH
• azacytidin farmakologie   MeSH
• biologické markery krev   metabolismus   MeSH
• chemokin CCL2 metabolismus   MeSH
• diferenciační antigeny krev   genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• interferon gama farmakologie   MeSH
• kompartmentace buňky účinky léků   MeSH
• kostní dřeň metabolismus   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• myelodysplastické syndromy krev   metabolismus   MeSH
• myeloidní buňky účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny krev   genetika   metabolismus   MeSH
• počet lymfocytů MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Acute myeloid leukaemia (AML) is the leading form of fatal acute leukaemia in adults. AML is a heterogeneous disease with respect to responsible mutations and chromosomal abnormalities as well as to their clinicopathological image. In recent years, great progress has been made in techniques allowing detection of genetic changes in both de novo AML and in secondary AML induced by other haematological disorders or therapy, and in detection of residual disease after therapy. Accumulated knowledge allowed better understanding of the molecules and mechanisms involved not only in the formation and expansion of a primary leukaemia-founding clone, but also of a temporal order of changes leading to the fully malignant phenotype. The recent knowledge of bone marrow (BM) compartments and interrelations among various BM resident and recruited cell types helps in understanding the AML development. The progress in the techniques and knowledge will result in the development and use of molecularly targeted therapies tailored to individual patient needs.

• MeSH
• akutní myeloidní leukemie genetika   metabolismus   MeSH
• chromozomální aberace MeSH
• fenotyp MeSH
• kostní dřeň metabolismus   MeSH
• lidé MeSH
• mutace genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Multiple myeloma, which ranks as the second most common hematological malignancy, is known for its great genetic heterogeneity. One pathway, however, stands out in this diverse group. NF-κB pathway is one of the most important pathways in multiple myeloma not only for its role in pathogenesis, but also for its importance in various treatment strategies. Mutations in several major components of the NF-κB pathway and its regulators are present in at least 17% of primary multiple myeloma tumors and 42% of multiple myeloma cell lines. The NF-κB pathway regulates numerous genes, which influence development and pathogenesis of multiple myeloma. This significance of NF-κB for myeloma cells, however, is used against them, as current treatment strategies often use NF-κB as their primary or secondary target.

• MeSH
• aktivace enzymů MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• cílená molekulární terapie MeSH
• kostní dřeň účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• management nemoci MeSH
• mnohočetný myelom diagnóza   etiologie   metabolismus   terapie   MeSH
• NF-kappa B antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Multiple myeloma (MM) is a highly heterogeneous disease of malignant plasma cells. Diagnosis and monitoring of MM patients is based on bone marrow biopsies and detection of abnormal immunoglobulin in serum and/or urine. However, biopsies have a single-site bias; thus, new diagnostic tests and early detection strategies are needed. Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry (MALDI-TOF MS) is a powerful method that found its applications in clinical diagnostics. Artificial intelligence approaches, such as Artificial Neural Networks (ANNs), can handle non-linear data and provide prediction and classification of variables in multidimensional datasets. In this study, we used MALDI-TOF MS to acquire low mass profiles of peripheral blood plasma obtained from MM patients and healthy donors. Informative patterns in mass spectra served as inputs for ANN that specifically predicted MM samples with high sensitivity (100%), specificity (95%) and accuracy (98%). Thus, mass spectrometry coupled with ANN can provide a minimally invasive approach for MM diagnostics.

• MeSH
• analýza hlavních komponent MeSH
• datové soubory jako téma MeSH
• imunoglobuliny krev   MeSH
• kostní dřeň metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické sítě a dráhy MeSH
• metabolom * MeSH
• mnohočetný myelom krev   diagnóza   patologie   MeSH
• neuronové sítě (počítačové) * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• studie případů a kontrol MeSH
• umělá inteligence * statistika a číselné údaje   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH