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Journal articles on the topic 'Haematopoietic'
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1
Kondera, Elżbieta. "Haematopoiesis and haematopoietic organs in fish." Roczniki Naukowe Polskiego Towarzystwa Zootechnicznego 15, no. 1 (March 31, 2019): 9–16. http://dx.doi.org/10.5604/01.3001.0013.4535.
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Haematopoiesis is a complex process in which haematopoietic stem cells, the most immature elements of the haematopoietic hierarchy, proliferate and differentiate into various classes of haematopoietic progenitor cells. These progenitor cells have been shown to be able to differentiate into mature blood cells: erythrocytes, lymphocytes, thrombocytes, granulocytes, and monocytes. The pronephros, or head kidney, is a basic organ forming the blood elements, and is also a reservoir of blood cells. Basic haematopoietic structures and mechanisms in fish are similar to those functioning in other vertebrates, and all haematopoietic cell types are very similar to those of mammals.
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De, Ranita, Kulkarni Uday Prakash, and Eunice S. Edison. "Complex Interactions in Regulation of Haematopoiesis—An Unexplored Iron Mine." Genes 12, no. 8 (August 20, 2021): 1270. http://dx.doi.org/10.3390/genes12081270.
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Iron is one of the most abundant metals on earth and is vital for the growth and survival of life forms. It is crucial for the functioning of plants and animals as it is an integral component of the photosynthetic apparatus and innumerable proteins and enzymes. It plays a pivotal role in haematopoiesis and affects the development and differentiation of different haematopoietic lineages, apart from its obvious necessity in erythropoiesis. A large amount of iron stores in humans is diverted towards the latter process, as iron is an indispensable component of haemoglobin. This review summarises the important players of iron metabolism and homeostasis that have been discovered in recent years and highlights the overall significance of iron in haematopoiesis. Its role in maintenance of haematopoietic stem cells, influence on differentiation of varied haematopoietic lineages and consequences of iron deficiency/overloading on development and maturation of different groups of haematopoietic cells have been discussed.
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Štefková, Kateřina, Markéta Hanáčková, Jan Kučera, Katarzyna Anna Radaszkiewicz, Barbora Ambrůžová, Lukáš Kubala, and Jiří Pacherník. "MAPK p38alpha Kinase Influences Haematopoiesis in Embryonic Stem Cells." Stem Cells International 2019 (June 2, 2019): 1–16. http://dx.doi.org/10.1155/2019/5128135.
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The activation of p38alpha kinase mediates cell response to various extracellular factors including many interleukins and growth factors important for haematopoiesis. The role of p38alpha kinase was previously analysed in particular haematopoietic cells. In this study and for the first time, the role of p38alpha kinase in haematopoiesis was studied using a model of continuous haematopoietic development in pluripotent embryonic stem cellsin vitro. The expression of transcripts associated with haematopoiesis and the potential for the formation of specific haematopoietic cell colonies were compared between wild-type and mutant p38alpha gene-depleted cells. The absence of p38alpha kinase led to the inhibition of hemangioblast formation during the first step of haematopoiesis. Later, during differentiation, due to the lack of p38alpha kinase, erythrocyte maturation was impaired. Mutant p38α−/−cells also exhibited decreased potential with respect to the expansion of granulocyte colony-forming units. This effect was reversed in the absence of erythropoietin as shown by colony-forming unit assay in media for colony-forming unit granulocytes/macrophages. p38alpha kinase thus plays an important role in the differentiation of common myeloid precursor cells into granulocyte lineages.
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Basden, K., DW Cooper, and EM Deane. "Development of the blood-forming tissues of the tammar wallaby Macropus eugenii." Reproduction, Fertility and Development 8, no. 6 (1996): 989. http://dx.doi.org/10.1071/rd9960989.
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The development of the haematopoietic tissues of the tammar wallaby Macropus eugenii follows a similar pattern to that observed in eutherian and other metatherian mammals. At birth, the liver appears to be the only site of haematopoiesis with significant numbers of neutrophils and stem cells present in the circulation. By Day 3, the spleen shows limited haematopoietic activity and by Day 12 contains areas of erythroid and myeloid cells. At two weeks after birth, the haematopoetic activity in the liver declines and small areas of haematopoiesis are apparent in the bone marrow. By the end of the first month, the bone marrow appears to be the major site of haematopoiesis.
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Al-Drees, Mohammad A., Jia Hao Yeo, Badwi B. Boumelhem, Veronica I. Antas, Kurt W. L. Brigden, Chanukya K. Colonne, and Stuart T. Fraser. "Making Blood: The Haematopoietic Niche throughout Ontogeny." Stem Cells International 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/571893.
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Approximately one-quarter of all cells in the adult human body are blood cells. The haematopoietic system is therefore massive in scale and requires exquisite regulation to be maintained under homeostatic conditions. It must also be able to respond when needed, such as during infection or following blood loss, to produce more blood cells. Supporting cells serve to maintain haematopoietic stem and progenitor cells during homeostatic and pathological conditions. This coalition of supportive cell types, organised in specific tissues, is termed the haematopoietic niche. Haematopoietic stem and progenitor cells are generated in a number of distinct locations during mammalian embryogenesis. These stem and progenitor cells migrate to a variety of anatomical locations through the conceptus until finally homing to the bone marrow shortly before birth. Under stress, extramedullary haematopoiesis can take place in regions that are typically lacking in blood-producing activity. Our aim in this review is to examine blood production throughout the embryo and adult, under normal and pathological conditions, to identify commonalities and distinctions between each niche. A clearer understanding of the mechanism underlying each haematopoietic niche can be applied to improvingex vivocultures of haematopoietic stem cells and potentially lead to new directions for transplantation medicine.
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Vainieri, Maria L., Andrew M. Blagborough, Adam L. MacLean, Myriam L. R. Haltalli, Nicola Ruivo, Helen A. Fletcher, Michael P. H. Stumpf, Robert E. Sinden, and Cristina Lo Celso. "Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points." Open Biology 6, no. 6 (June 2016): 160038. http://dx.doi.org/10.1098/rsob.160038.
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Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1 + progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host.
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Haznedaroglu, Ibrahim C., and Yavuz Beyazit. "Local bone marrow renin–angiotensin system in primitive, definitive and neoplastic haematopoiesis." Clinical Science 124, no. 5 (November 12, 2012): 307–23. http://dx.doi.org/10.1042/cs20120300.
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The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin–angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34+ BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.
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Keenan, Christine R. "Heterochromatin and Polycomb as regulators of haematopoiesis." Biochemical Society Transactions 49, no. 2 (April 30, 2021): 805–14. http://dx.doi.org/10.1042/bst20200737.
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Haematopoiesis is the process by which multipotent haematopoietic stem cells are transformed into each and every type of terminally differentiated blood cell. Epigenetic silencing is critical for this process by regulating the transcription of cell-cycle genes critical for self-renewal and differentiation, as well as restricting alternative fate genes to allow lineage commitment and appropriate differentiation. There are two distinct forms of transcriptionally repressed chromatin: H3K9me3-marked heterochromatin and H3K27me3/H2AK119ub1-marked Polycomb (often referred to as facultative heterochromatin). This review will discuss the role of these distinct epigenetic silencing mechanisms in regulating normal haematopoiesis, how these contribute to age-related haematopoietic dysfunction, and the rationale for therapeutic targeting of these pathways in the treatment of haematological malignancies.
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HARMS, Gesche, Regine KRAFT, Gerlinde GRELLE, Bärbel VOLZ, Jens DERNEDDE, and Rudolf TAUBER. "Identification of nucleolin as a new L-selectin ligand." Biochemical Journal 360, no. 3 (December 10, 2001): 531–38. http://dx.doi.org/10.1042/bj3600531.
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Apart from leucocyte–endothelial interactions, the adhesion molecule L-selectin mediates the homotypic adhesion of leucocytes during recruitment at sites of acute inflammation, as well as intercellular adhesion of haematopoietic progenitor cells during haematopoiesis. There is evidence that, in addition to P-selectin glycoprotein ligand-1, other as-yet-unidentified proteins function as L-selectin ligands on human leucocytes and haematopoietic progenitor cells. In the present study, we show: (i) by affinity chromatography on L-selectin–agarose; (ii) by protein identification using MS; and (iii) by covalent cell-surface labelling with sulphosuccinimidyl-2-(biotinamido)ethyl-1,3-dithiopropionate that the multifunctional nuclear protein nucleolin is partly exposed on the cell surface, and is a ligand of L-selectin in human leucocytes and haematopoietic progenitor cells.
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Karia, Dimple, Robert C. G. Gilbert, Antonio J. Biasutto, Catherine Porcher, and Erika J. Mancini. "The histone H3K4 demethylase JARID1A directly interacts with haematopoietic transcription factor GATA1 in erythroid cells through its second PHD domain." Royal Society Open Science 7, no. 1 (January 2020): 191048. http://dx.doi.org/10.1098/rsos.191048.
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Chromatin remodelling and transcription factors play important roles in lineage commitment and development through control of gene expression. Activation of selected lineage-specific genes and repression of alternative lineage-affiliated genes result in tightly regulated cell differentiation transcriptional programmes. However, the complex functional and physical interplay between transcription factors and chromatin-modifying enzymes remains elusive. Recent evidence has implicated histone demethylases in normal haematopoietic differentiation as well as in malignant haematopoiesis. Here, we report an interaction between H3K4 demethylase JARID1A and the haematopoietic-specific master transcription proteins SCL and GATA1 in red blood cells. Specifically, we observe a direct physical contact between GATA1 and the second PHD domain of JARID1A. This interaction has potential implications for normal and malignant haematopoiesis.
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Mak, Ka Sin, Alister P. W. Funnell, Richard C. M. Pearson, and Merlin Crossley. "PU.1 and Haematopoietic Cell Fate: Dosage Matters." International Journal of Cell Biology 2011 (2011): 1–6. http://dx.doi.org/10.1155/2011/808524.
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The ETS family transcription factor PU.1 is a key regulator of haematopoietic differentiation. Its expression is dynamically controlled throughout haematopoiesis in order to direct appropriate lineage specification. Elucidating the biological role of PU.1 has proved challenging. This paper will discuss how a range of experiments in cell lines and mutant and transgenic mouse models have enhanced our knowledge of the mechanisms by which PU.1 drives lineage-specific differentiation during haematopoiesis.
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Dickson, M. C., J. S. Martin, F. M. Cousins, A. B. Kulkarni, S. Karlsson, and R. J. Akhurst. "Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice." Development 121, no. 6 (June 1, 1995): 1845–54. http://dx.doi.org/10.1242/dev.121.6.1845.
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Transforming growth factor beta 1 (TGF beta 1) is shown here to be required for yolk sac haematopoiesis and endothelial differentiation. Mice with a targeted mutation in the TGF beta 1 gene were examined to determine the cause of prenatal lethality, which occurs in 50% of homozygous TGF beta 1 null (TGF beta 1−/−) conceptions. 50% of TGF beta 1−/− and 25% of TGF beta 1-+-) conceptions. 50% of TGF beta 1−/− and 25% of TGF beta 1+/− conceptuses were found to die at around 10.5 dpc. The primary defects were restricted to extraembryonic tissues, namely the yolk sac vasculature and haematopoietic system. The embryos per se showed developmental retardation, oedema and necrosis, which were probably secondary to the extraembryonic lesions. The defect in vasculogenesis appeared to affect endothelial differentiation, rather than the initial appearance and outgrowth of endothelial cells. Initial differentiation of yolk sac mesoderm to endothelial cells occurred, but defective differentiation resulted in inadequate capillary tube formation, and weak vessels with reduced cellular adhesiveness. Defective haematopoiesis resulted in a reduced erythroid cell number within the yolk sac. Defective yolk sac vasculogenesis and haematopoiesis were present either together, or in isolation of each other. The phenotypes are consistent with the observation of abundant TGF beta 1 gene expression in both endothelial and haematopoietic precursors. The data indicate that the primary effect of loss of TGF beta 1 function in vivo is not increased haematopoietic or endothelial cell proliferation, which might have been expected by deletion of a negative growth regulator, but defective haematopoiesis and endothelial differentiation.
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Sánchez, María-José, Ernesto-Otto Bockamp, Jane Miller, Laure Gambardella, and Anthony R. Green. "Selective rescue of early haematopoietic progenitors in Scl–/– mice by expressing Scl under the control of a stem cell enhancer." Development 128, no. 23 (December 1, 2001): 4815–27. http://dx.doi.org/10.1242/dev.128.23.4815.
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The stem cell leukaemia gene (Scl) encodes a basic helix-loop-helix transcription factor with a pivotal role in both haematopoiesis and endothelial development. During mouse development, Scl is first expressed in extra-embryonic mesoderm, and is required for the generation of all haematopoietic lineages and normal yolk sac angiogenesis. Ectopic expression of Scl during zebrafish development specifies haemangioblast formation from early mesoderm. These results suggest that SCL is essential for establishing the transcriptional programme responsible for the formation of haematopoietic stem cells and have focused attention on the transcriptional regulation of Scl itself. Previous studies have identified a panel of Scl enhancers each of which directed expression to a subdomain of the normal Scl expression pattern. Among them, a 3′ enhancer directed expression during development to vascular endothelium and haematopoietic progenitors but not to Ter119+ erythroid cells. The expression in haematopoietic stem cells, however, remained undetermined. We demonstrate that this 3′ enhancer directs lacZ expression in transgenic mice to most foetal and adult long-term repopulating haematopoietic stem cells, and therefore functions as a stem cell enhancer. Consistent with these results, expression in Scl–/– embryos of exogenous Scl driven by the stem cell enhancer rescued the formation of early haematopoietic progenitors and also resulted in normal yolk sac angiogenesis. By contrast, erythropoiesis remained markedly deficient in rescued embryos. This observation is consistent with the inactivity of the stem cell enhancer in erythroid cells and reveals an essential role for SCL during erythroid differentiation in vivo.
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Groner, Yoram, Pnina Sachs, and Joseph Lotem. "Leo Sachs. 14 October 1924—12 December 2013." Biographical Memoirs of Fellows of the Royal Society 66 (February 13, 2019): 355–75. http://dx.doi.org/10.1098/rsbm.2018.0027.
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Leo Sachs was a worldwide renowned scientist for his major contributions in several fields. In the mid 1950s he showed that amniocentesis could be used for prenatal diagnosis of sex and blood group antigens. He then focused on various aspects of normal development and cancer, including the control of normal haematopoiesis and leukaemia, carcinogenesis in vitro by polyoma and SV40 tumour viruses, chemical carcinogens and X-rays, chromosomes and the reversibility of cancer, surface membrane changes in malignant cells and suppression of malignancy by inducing differentiation. The cell culture system he established in the early 1960s for the clonal development of normal haematopoietic cells made it possible to analyse the molecular basis of normal haematopoiesis, and discover the proteins that regulate viability, proliferation and differentiation of different blood cell lineages and the changes that drive leukaemia. His studies established significant general concepts, including: the differential responsiveness of cancer cells to normal regulators of development; suppression of myeloid leukaemia by inducing differentiation, bypassing malignancy-driving genetic defects; identification of chromosomes that control tumour suppression; discovering apoptosis as a major mechanism by which WT-p53 suppresses malignancy; and the ability of haematopoietic cytokines to suppress apoptosis in both normal and leukaemic cells. Leo was fortunate to witness his pioneering discoveries and ideas move from the basic science stage to effective clinical applications, using amniocentesis for prenatal detection of genetic abnormalities, augmenting normal haematopoiesis in patients with various haematopoietic deficiencies and suppressing malignancy by inducing differentiation and apoptosis.
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Thorpe, Robin, and Meenu Wadhwa. "Haematopoietic growth factors and their therapeutic use." Thrombosis and Haemostasis 99, no. 11 (2008): 863–73. http://dx.doi.org/10.1160/th07-11-0703.
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SummaryHaematopoietic growth factors constitute an important group of proteins that predominantly regulate the process of haematopoiesis. While some of these proteins have a very broad array of action on very early haematopoietic progenitors leading to multi-lineage increases in haematopoietic cell production and differentiation, others act in a restricted manner on specific committed terminally differentiated cell types. On the basis of their unique spectrum of activities, several factors are approved for clinical use in various indications while others are under investigation in the clinic either alone or as combination therapy. In this review, we have described factors which directly and in some cases indirectly influence haematopoiesis with particular focus on those factors which are either approved or show potential for clinical use. A brief description of the products that are currently available for clinical use is also provided. At present, several new products which include fusion proteins, peptide mimetics are either at the pre-clinical stage or in clinical development for various indications and these are also briefly described.
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Manesso, Erica, José Teles, David Bryder, and Carsten Peterson. "Dynamical modelling of haematopoiesis: an integrated view over the system in homeostasis and under perturbation." Journal of The Royal Society Interface 10, no. 80 (March 6, 2013): 20120817. http://dx.doi.org/10.1098/rsif.2012.0817.
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A very high number of different types of blood cells must be generated daily through a process called haematopoiesis in order to meet the physiological requirements of the organism. All blood cells originate from a population of relatively few haematopoietic stem cells residing in the bone marrow, which give rise to specific progenitors through different lineages. Steady-state dynamics are governed by cell division and commitment rates as well as by population sizes, while feedback components guarantee the restoration of steady-state conditions. In this study, all parameters governing these processes were estimated in a computational model to describe the haematopoietic hierarchy in adult mice. The model consisted of ordinary differential equations and included negative feedback regulation. A combination of literature data, a novel divide et impera approach for steady-state calculations and stochastic optimization allowed one to reduce possible configurations of the system. The model was able to recapitulate the fundamental steady-state features of haematopoiesis and simulate the re-establishment of steady-state conditions after haemorrhage and bone marrow transplantation. This computational approach to the haematopoietic system is novel and provides insight into the dynamics and the nature of possible solutions, with potential applications in both fundamental and clinical research.
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Denizot, Y., and V. Praloran. "PAF and Haematopoiesis. I. 5-Fluoro-Uracil Induces PAF Production in Haematopoietic Organs of Rats." Mediators of Inflammation 3, no. 1 (1994): 23–25. http://dx.doi.org/10.1155/s0962935194000049.
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Haematopoietic organs of rats were examined for the presence of platelet-activating factor (PAF) and acetylhydrolase before and after treatment with 5-fluoro-uracil (5-FU) (200 mg/kg) a chemotherapeutic compound with apoptotic effects. PAF was reported in thymus, spleen and femoral bone marrow of rats with or without 5-FU. Although acetylhydrolase activity in organs was not affected by 5-FU treatment, elevated levels of PAF were observed in thymus and spleen. For the first time PAF is reported in haematopoietic organs of rats, strengtheningin vitrodata suggesting its role in the apoptotic processes in thymus, in the modulation of the immune response, and in the regulation of haematopoiesis.
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Fouillard, Loic, Alain Chapel, Domnique Bories, Sandrine Bouchet Tec, Helene Rouard, Patrick Herve, Patrick Gourmelon, Dominique Thierry, and Norbert C. Gorin. "Allogeneic Related HLA Mismatch Mesenchymal Stem Cells for the Treatment of Engraftment Failure Following Autologous Hematopoietic Stem Cell Transplantation." Blood 108, no. 11 (November 16, 2006): 2560. http://dx.doi.org/10.1182/blood.v108.11.2560.2560.
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Abstract Primary graft failure is usually associated with a high mortality rate despite infusion of back up graft and haematopoietic growth factors. In animal models mesenchymal stem cells (MSC) stimulate haematopoiesis recovery after TBI and enhance engraftment of haematopoietic stem cells (Almeida-Porada et al, Exp hematol 1999). Co-infusion of autologous blood stem cells and MSC in cancer patients receiving high dose chemotherapy speed up haematopoietic recovery (Koç et al, JCO 2000). We have previously shown that MSC can engraft and improve the bone marrow microenvironment in a patient with end stage severe aplastic anaemia (Fouillard et al, Leukemia 2003). We report a patient treated with MSC for aplastic anemia secondary to engraftment failure. A 40 year old nulliparous woman with acute myeloid leukaemia received an autologous bone marrow transplantation; conditioning regimen combined a 12 Gray TBI and cyclophosphamide (120 mg/kg). Primary graft failure occurred and persited despite back up marrow infusion. Partial recovery on polymorphonuclear (PMN) and haemoglobin (Hb) was obtained with granulocyte colony stimulating factor (G-CSF) and EPO. Thrombocytopenia remained below 50x109/l. No residual leukaemic cells were detected Three years after ABMT, allogeneic MSC were infused at a dose of 2,78x106/kg. MSC were isolated from a HLA mismatched brother bone marrow (Osiris Therapeutics Inc Baltimore, MD). At time of MSC infusion, the marrow aspirate was hypocellular with no leukaemic blast cells. Blood cell counts were: PMN: 0.8x109/l, platelets: 45x109/l and Hb: 10.5 g/dl. No conditioning regimen and no prophylaxis of GVHD was given. Growth factors were discontinued. After MSC infusion, a rapid haematopoietic recovery was observed on both PMN and platelet which reached a normal level. With a follow up of 18 months, the patient is alive and well. Recovery of haematopoiesis was corroborated by an improvement of in vitro haematopoietic and stromal clonogenic assays. CFU-GM and CFU-F studied the day before MSC infusion, one month and one year after MSC infusion, increased strikingly (p<0.05). LTC-IC increased significantly one year after MSC infusion (p<0.05). There was no change in BFUE. To further characterize the effects seen on haematopoiesis, we utilized a custom RayBiotech antibody array and compared proteins secreted by MSC of recipient before and one year after infusion. This array evidenced an increased secretion of proteins implied in haematopoiesis (Flt3l, GM-CSF, G-CSF, IL1, IL6, TPO, SDF1) one year after MSC infusion. Real time PCR confirmed an up-regulation of gene expression for GCSF, GM-CSF, IL1, IL6. We studied MSC engraftment. We analysed the bone marrow biopsy extracted DNA for mesenchymal chimerism before MSC infusion, one month and one year post MSC infusion by real time quantitative PCR of the Y specific SRY gene: male DNA was not detected before infusion; a level of male DNA of 1/105 was detected one month after MSC infusion. This observation shows that MSC can induce haematopoietic tissue repair. MSC should be considered in the treatment of engraftment failure and other bone marrow failure states including severe idiopathic aplastic anaemia and accidental irradiation.
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Sanchez, M., B. Gottgens, A. M. Sinclair, M. Stanley, C. G. Begley, S. Hunter, and A. R. Green. "An SCL 3′ enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors." Development 126, no. 17 (September 1, 1999): 3891–904. http://dx.doi.org/10.1242/dev.126.17.3891.
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The SCL gene encodes a basic helix-loop-helix transcription factor which is expressed in early haematopoietic progenitors throughout ontogeny and is essential for the normal development of blood and blood vessels. Transgenic studies have characterised spatially distinct 5′ enhancers which direct lacZ expression to subdomains of the normal SCL expression pattern, but the same elements failed to produce appropriate haematopoietic expression. We now describe an SCL 3′ enhancer with unique properties. It directed lacZ expression in transgenic mice to extra-embryonic mesoderm and subsequently to both endothelial cells and to a subset of blood cells at multiple sites of embryonic haematopoiesis including the yolk sac, para-aortic splanchnopleura and AGM region. The 3′ enhancer also targeted expression to haematopoietic progenitors in both foetal liver and adult bone marrow. Purified lacZ(+)cells were highly enriched for clonogenic myeloid and erythroid progenitors as well as day-12 spleen colony forming units (CFU-S). Within the total gated population from bone marrow, 95% of the myeloid and 90% of the erythroid colony-forming cells were contained in the lacZ(+) fraction, as were 98% of the CFU-S. Activation of the enhancer did not require SCL protein. On the contrary, transgene expression in yolk sacs was markedly increased in an SCL−/− background, suggesting that SCL is subject to negative autoregulation. Alternatively the SCL−/− environment may alter differentiation of extra-embryonic mesoderm and result in an increased number of cells capable of expressing high levels of the transgene. Our data represents the first description of an enhancer that integrates information necessary for expression in developing endothelium and early haematopoietic progenitors at distinct times and sites throughout ontogeny. This enhancer provides a potent tool for the manipulation of haematopoiesis and vasculogenesis in vivo.
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Göttgens, Berthold, Ian J. Donaldson, Michael Chapman, Sarah Kinston, Josette Renée Landry, Kathy Knezevic, Sandie Piltz, Noel Buckley, and Anthony Green. "Genome-Wide Identification of Cis-Regulatory Sequences Controlling Blood and Endothelial Development." Blood 104, no. 11 (November 16, 2004): 1616. http://dx.doi.org/10.1182/blood.v104.11.1616.1616.
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Abstract Haematopoiesis has long served as a paradigm for adult stem cell systems and studies over the last 20 years have established that transcriptional control is central to the specification and subsequent differentiation of haematopoietic stem cells (HSCs). With many of the key transcription factors known, haematopoiesis provides a powerful cellular system for the analysis of mammalian gene regulatory networks. The key missing ingredient, particularly for the stem and progenitor cell stages, is a set of experimentally validated gene regulatory regions together with a molecular understanding of their biological activity. Despite progress in lower organisms, genome-wide computational identification of mammalian cis-regulatory sequences has been hindered by increased genomic complexity and cumbersome transgenic assays. In order to identify transcriptional control regions active during early embryonic haematopoietic development, we have developed a strategy that is based upon a haematopoietic stem cell enhancer (+19 enhancer) identified downstream of the SCL transcription factor, a key regulator of haematopoietic stem cell formation. Starting with this well-characterised blood stem cell enhancer, we have developed computational tools which allow genome-wide identification of functionally related enhancers. This approach has been used to identify novel enhancers involved in the regulation of early blood and endothelial development, and which exhibit predicted biological activity in vitro and in transgenic mice. Transcription factors binding to these enhancers have been identified by chromatin immunoprecipitation. Our data allow the construction of an experimentally verified nascent transcriptional network, which controls the development of blood and endothelium, and which so far contains the SCL, GATA-2, Fli-1, Elf-1 and Hex transcription factors. Additional candidate members of the network have been identified and are being subjected to functional validation. This approach represents a widely applicable strategy for characterising the transcriptional networks controlling a broad range of mammalian developmental programmes.
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Oliveira, Dalila Cunha, Amanda Nogueira-Pedro, Ed Wilson Santos, Araceli Hastreiter, Graziela Batista Silva, Primavera Borelli, and Ricardo Ambrósio Fock. "A review of select minerals influencing the haematopoietic process." Nutrition Research Reviews 31, no. 2 (July 9, 2018): 267–80. http://dx.doi.org/10.1017/s0954422418000112.
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AbstractMicronutrients are indispensable for adequate metabolism, such as biochemical function and cell production. The production of blood cells is named haematopoiesis and this process is highly consuming due to the rapid turnover of the haematopoietic system and consequent demand for nutrients. It is well established that micronutrients are relevant to blood cell production, although some of the mechanisms of how micronutrients modulate haematopoiesis remain unknown. The aim of the present review is to summarise the effect of Fe, Mn, Ca, Mg, Na, K, Co, iodine, P, Se, Cu, Li and Zn on haematopoiesis. This review deals specifically with the physiological requirements of selected micronutrients to haematopoiesis, showing various studies related to the physiological requirements, deficiency or excess of these minerals on haematopoiesis. The literature selected includes studies in animal models and human subjects. In circumstances where these minerals have not been studied for a given condition, no information was used. All the selected minerals have an important role in haematopoiesis by influencing the quality and quantity of blood cell production. In addition, it is highly recommended that the established nutrition recommendations for these minerals be followed, because cases of excess or deficient mineral intake can affect the haematopoiesis process.
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Qiu, Xi, Xiang-Gui Yuan, Xiao-li Jin, Xin He, Lei Zhu, and Xiao-Ying Zhao. "Oestrogen-deficiency inducing haematopoiesis dysfunction via reduction in haematopoietic stem cells and haematopoietic growth factors in rats." International Journal of Experimental Pathology 93, no. 3 (May 14, 2012): 179–87. http://dx.doi.org/10.1111/j.1365-2613.2012.00815.x.
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Almohamad, Khaled M., and Fatima M. Alsheikh. "The relationship between the alkaline phosphatase network and the haematopoiesis in mice subjected to whole-body irradiation." Nukleonika 59, no. 3 (August 1, 2014): 105–10. http://dx.doi.org/10.2478/nuka-2014-0012.
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Abstract Purpose: To investigate the relationship between the alkaline phosphatase (ALP) network of the marrow stroma and the haematopoietic regeneration after mice whole-body irradiation. Materials and methods: Three groups of mice were irradiated with a non-lethal ionising radiation dose: the fi rst one received an intraperitoneal injection of Levamisole, ALP inhibitor, 24 h before irradiation; the second one received an intraperitoneal injection of Lisinopril, haematopoiesis inhibitor, 24 h before irradiation; the third was left untreated, but irradiated. The fourth group, untreated and not irradiated, was the control. The total surface occupied by ALP positive processes, revealed by means of ALP cytochemistry in the marrow area, was evaluated semi-quantitively. Nucleated bone marrow cells were also counted. Results: ALP network began to increase 24 h after irradiation to reach a maximum after 72 h, when the bone marrow was almost become completely empty of the haematopoietic cells. This increase advances the haematopoietic recovery. This process was substantially delayed when the mice were injected with Levamisole 24 h before irradiation. On the contrary, ALP network increased strongly since the fi rst day after irradiation when the mice were injected with Lisinopril 24 h before irradiation. Conclusions: These data have indicated that the haematopoietic recovery and repopulation of the bone marrow were advanced by the ALP network recovery.
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Forrester, A. Michael, Jason N. Berman, and Elspeth M. Payne. "Myelopoiesis and Myeloid Leukaemogenesis in the Zebrafish." Advances in Hematology 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/358518.
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Over the past ten years, studies using the zebrafish model have contributed to our understanding of vertebrate haematopoiesis, myelopoiesis, and myeloid leukaemogenesis. Novel insights into the conservation of haematopoietic lineages and improvements in our capacity to identify, isolate, and culture such haematopoietic cells continue to enhance our ability to use this simple organism to address disease biology. Coupled with the strengths of the zebrafish embryo to dissect developmental myelopoiesis and the continually expanding repertoire of models of myeloid malignancies, this versatile organism has established its niche as a valuable tool to address key questions in the field of myelopoiesis and myeloid leukaemogenesis. In this paper, we address the recent advances and future directions in the field of myelopoiesis and leukaemogenesis using the zebrafish system.
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Ansell, J. D., K. Samuel, D. G. Whittingham, C. E. Patek, K. Hardy, A. H. Handyside, K. W. Jones, A. L. Muggleton-Harris, A. H. Taylor, and M. L. Hooper. "Hypoxanthine phosphoribosyl transferase deficiency, haematopoiesis and fertility in the mouse." Development 112, no. 2 (June 1, 1991): 489–98. http://dx.doi.org/10.1242/dev.112.2.489.
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We have looked for effects of deficiency in hypoxanthine phosphoribosyl transferase (HPRT) in the mouse comparable to non-behavioural consequences of HPRT-deficiency in humans. HPRT-deficient humans show abnormalities in haematopoiesis and, in heterozygotes, there is strong selection in haematopoietic tissues against HPRT-deficient cells arising as a result of X-chromosome inactivation. We have examined two situations in mice in which HPRT- and HPRT+ cells occur in the same individual. First, in chimaeras resulting from the injection of HPRT- embryonal stem cells into HPRT+ blastocysts the fate of HPRT- and HPRT+ cell populations was monitored by their expression of different isozymes of glucose phosphate isomerase and also, in those chimaeras that resulted from injecting the male ES cells into female blastocysts, by in situ hybridisation using a Y-chromosome-specific repetitive DNA probe. There was a small statistically significant selection against the HPRT- population in haematopoietic tissues in both XX in equilibrium with XY and XY in equilibrium with XY chimaeras. Second, in female mice doubly heterozygous for HPRT-deficiency and for an electrophoretic variant of the X-linked enzyme phosphoglycerate kinase, there was a similar small statistically significant selection against the HPRT- population in haematopoietic tissues. While further work is required to establish whether this selection is a consequence of the HPRT mutation, it is clear that any selection against cells in the haematopoietic system as a consequence of HPRT-deficiency is at most small compared with the effect seen in humans. In HPRT-deficient human males surviving beyond the normal age of puberty, there is testicular atrophy. However, we find no effect of HPRT-deficiency on the fertility of either male or female mice. Thus, as with effects on behaviour, the consequences of HPRT-deficiency for haematopoiesis and testis development in the mouse are at most small compared with those in the human. We conclude that the reason for the difference in effects between the two species lies in a difference in purine-related intermediary metabolism per se, rather than in its interaction with brain amine biochemistry.
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Erlacher, Miriam, Daniela Bertele, Claudia Woess, Charlotte Marie Niemeyer, Andreas Villunger, and Verena Labi. "Lack of the BH3-Only Proteins Bim, Bmf and Puma In Haematopoietic Stem and Progenitor Cells Facilitates Early Reconstitution and Long Term Haematopoiesis." Blood 116, no. 21 (November 19, 2010): 1542. http://dx.doi.org/10.1182/blood.v116.21.1542.1542.
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Abstract Abstract 1542 During haematopoietic stem cell transplantation (HSCT) the transplanted haematopoietic stem and progenitor cells (HSPC) suffer a transient deprivation of survival signals (i.e. cytokines or adhesion molecules) normally provided by the stem cell niche. Therefore, cell loss may occur prior to successful engraftment and thus restrict haematopoietic reconstitution. Apoptosis induced in response to lack of cytokines or contact to the extracellular matrix is regulated by members of the Bcl-2 family. Bcl-2 family members can be divided into the pro-apoptotic ‘BH3-only’ proteins and anti-apoptotic Bcl-2 like proteins, the two subclasses antagonizing each other in their function. Using different gene-modified mouse models lacking the ‘BH3-only’ proteins Bim, Bmf or Puma, all implicated in leukocyte homeostasis, we aimed to delineate which one of these Bcl-2 family proteins is critically involved in limiting successful reconstitution of the haematopoietic system. Our results demonstrate that HSPC lacking Bim show accelerated reconstitution of lethally irradiated recipient mice. Moreover, competitive reconstitution experiments reveal that wild type haematopoiesis is completely displaced in wt:bim-/- and strongly suppressed in wt:bmf-/- and wt:puma-/- bone marrow chimeras. The effects of Bim are comparable to those observed upon induced overexpression of Bcl-2 and cannot be enhanced further by additional loss of Puma or Bmf, identifying Bim as the major BH3-only protein limiting cell survival during haematopoiesis. Since both lymphopoiesis and myelopoiesis are similarly affected, a direct role of Bim on early progenitor or even stem cells can be assumed. However, wild type lymphocytes are additionally outcompeted by bim-/- and bcl-2 tg lymphocytes during differentiation, since the balance between Bim and Bcl-2 is critically involved in many selection processes occurring during a lymphocyte's life (i.e. negative selection in the thymus). In summary, inhibition of apoptosis in HSPC by transiently interfering with Bim-function may be a promising strategy to increase the efficacy of HSCT and reduce transplantation-related morbidity. Disclosures: No relevant conflicts of interest to declare.
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Fadini, Gian Paolo, Anurag Mehta, Devinder Singh Dhindsa, Benedetta Maria Bonora, Gopalkrishna Sreejit, Prabhakara Nagareddy, and Arshed Ali Quyyumi. "Circulating stem cells and cardiovascular outcomes: from basic science to the clinic." European Heart Journal 41, no. 44 (December 31, 2019): 4271–82. http://dx.doi.org/10.1093/eurheartj/ehz923.
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Abstract The cardiovascular and haematopoietic systems have fundamental inter-relationships during development, as well as in health and disease of the adult organism. Although haematopoietic stem cells (HSCs) emerge from a specialized haemogenic endothelium in the embryo, persistence of haemangioblasts in adulthood is debated. Rather, the vast majority of circulating stem cells (CSCs) is composed of bone marrow-derived HSCs and the downstream haematopoietic stem/progenitors (HSPCs). A fraction of these cells, known as endothelial progenitor cells (EPCs), has endothelial specification and vascular tropism. In general, the levels of HSCs, HSPCs, and EPCs are considered indicative of the endogenous regenerative capacity of the organism as a whole and, particularly, of the cardiovascular system. In the last two decades, the research on CSCs has focused on their physiologic role in tissue/organ homoeostasis, their potential application in cell therapies, and their use as clinical biomarkers. In this review, we provide background information on the biology of CSCs and discuss in detail the clinical implications of changing CSC levels in patients with cardiovascular risk factors or established cardiovascular disease. Of particular interest is the mounting evidence available in the literature on the close relationships between reduced levels of CSCs and adverse cardiovascular outcomes in different cohorts of patients. We also discuss potential mechanisms that explain this association. Beyond CSCs’ ability to participate in cardiovascular repair, levels of CSCs need to be interpreted in the context of the broader connections between haematopoiesis and cardiovascular function, including the role of clonal haematopoiesis and inflammatory myelopoiesis.
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Cuthbertson, Peter, Nicholas J. Geraghty, Sam R. Adhikary, Katrina M. Bird, Stephen J. Fuller, Debbie Watson, and Ronald Sluyter. "Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease." International Journal of Molecular Sciences 22, no. 15 (August 3, 2021): 8343. http://dx.doi.org/10.3390/ijms22158343.
Full textAbstract:
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for blood cancers and other haematological disorders. However, allo-HSCT leads to graft-versus-host disease (GVHD), a severe and often lethal immunological response, in the majority of transplant recipients. Current therapies for GVHD are limited and often reduce the effectiveness of allo-HSCT. Therefore, pro- and anti-inflammatory factors contributing to disease need to be explored in order to identify new treatment targets. Purinergic signalling plays important roles in haematopoiesis, inflammation and immunity, and recent evidence suggests that it can also affect haematopoietic stem cell transplantation and GVHD development. This review provides a detailed assessment of the emerging roles of purinergic receptors, most notably P2X7, P2Y2 and A2A receptors, and ectoenzymes, CD39 and CD73, in GVHD.
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Carmichael, Catherine L., and Jody J. Haigh. "The Snail Family in Normal and Malignant Haematopoiesis." Cells Tissues Organs 203, no. 2 (2017): 82–98. http://dx.doi.org/10.1159/000448655.
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Snail family proteins are key inducers of the epithelial-mesenchymal transition (EMT), a critical process required for normal embryonic development. They have also been strongly implicated in regulating the EMT-like processes required for tumour cell invasion, migration, and metastasis. Whether these proteins also contribute to normal blood cell development, however, remains to be clearly defined. Increasing evidence supports a role for the Snail family in regulating cell survival, migration, and differentiation within the haematopoietic system, as well as potentially an oncogenic role in the malignant transformation of haematopoietic stem cells. This review will provide a broad overview of the Snail family, including key aspects of their involvement in the regulation and development of solid organ cancer, as well as a discussion on our current understanding of Snail family function during normal and malignant haematopoiesis.
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Cuvertino, Sara, Georges Lacaud, and Valerie Kouskoff. "SOX7-enforced expression promotes the expansion of adult blood progenitors and blocks B-cell development." Open Biology 6, no. 7 (July 2016): 160070. http://dx.doi.org/10.1098/rsob.160070.
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During embryogenesis, the three SOXF transcription factors, SOX7, SOX17 and SOX18, regulate the specification of the cardiovascular system and are also involved in the development of haematopoiesis. The ectopic expression of SOX17 in both embryonic and adult blood cells enhances self-renewal. Likewise, the enforced expression of SOX7 during embryonic development promotes the proliferation of early blood progenitors and blocks lineage commitment. However, whether SOX7 expression can also affect the self-renewal of adult blood progenitors has never been explored. In this study, we demonstrate using an inducible transgenic mouse model that the enforced expression of Sox7 ex vivo in bone marrow/stroma cell co-culture promotes the proliferation of blood progenitors which retain multi-lineage short-term engrafting capacity. Furthermore, SOX7 expression induces a profound block in the generation of B lymphocytes. Correspondingly, the ectopic expression of SOX7 in vivo results in dramatic alterations of the haematopoietic system, inducing the proliferation of blood progenitors in the bone marrow while blocking B lymphopoiesis. In addition, SOX7 expression induces extra-medullary haematopoiesis in the spleen and liver. Together, these data demonstrate that the uncontrolled expression of the transcription factor SOX7 in adult haematopoietic cells has dramatic consequences on blood homeostasis.
31
Guimaraes, M. J., J. F. Bazan, A. Zlotnik, M. V. Wiles, J. C. Grimaldi, F. Lee, and T. McClanahan. "A new approach to the study of haematopoietic development in the yolk sac and embryoid bodies." Development 121, no. 10 (October 1, 1995): 3335–46. http://dx.doi.org/10.1242/dev.121.10.3335.
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To understand the mechanisms that control the differentiation of uncommitted mesoderm precursors into haematopoietic stem cells (HSCs) and the activation of haematopoiesis, we conducted a study to identify genes expressed at the earliest stages of both in vivo and in vitro haematopoietic development. Our strategy was to utilize Differential Display by means of the Polymerase Chain Reaction (DD-PCR) to compare patterns of gene expression between mRNA populations representing different levels of haematopoietic activity obtained from the mouse embryo, embryoid bodies (EBs) and mouse cell lines. We report the molecular cloning of two groups of genes expressed in the yolk sac: a group of genes expressed in the day-8.5 yolk sac at higher levels than in the day-8.5 embryo proper and up-regulated during EB development, and another group of day-8.5 yolk sac genes not expressed in the day-8.5 embryo proper or in EBs. Specifically, we describe the molecular cloning of the first nucleobase permease gene to be found in vertebrates, yolk sac permease-like molecule 1 (Ysp11). The Ysp11 gene has the unique property of encoding both intracellular, transmembrane and extracellular protein forms, revealing novel aspects of nucleotide metabolism that may be relevant during mammalian development.
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Buisman, Sonja C., and Gerald de Haan. "Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies." Cells 8, no. 8 (August 10, 2019): 868. http://dx.doi.org/10.3390/cells8080868.
Full textAbstract:
Aging is associated with multiple molecular and functional changes in haematopoietic cells. Most notably, the self-renewal and differentiation potential of hematopoietic stem cells (HSCs) are compromised, resulting in myeloid skewing, reduced output of red blood cells and decreased generation of immune cells. These changes result in anaemia, increased susceptibility for infections and higher prevalence of haematopoietic malignancies. In HSCs, age-associated global epigenetic changes have been identified. These epigenetic alterations in aged HSCs can occur randomly (epigenetic drift) or are the result of somatic mutations in genes encoding for epigenetic proteins. Mutations in loci that encode epigenetic modifiers occur frequently in patients with haematological malignancies, but also in healthy elderly individuals at risk to develop these. It may be possible to pharmacologically intervene in the aberrant epigenetic program of derailed HSCs to enforce normal haematopoiesis or treat age-related haematopoietic diseases. Over the past decade our molecular understanding of epigenetic regulation has rapidly increased and drugs targeting epigenetic modifications are increasingly part of treatment protocols. The reversibility of epigenetic modifications renders these targets for novel therapeutics. In this review we provide an overview of epigenetic changes that occur in aging HSCs and age-related malignancies and discuss related epigenetic drugs.
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Vávrová, Jiřina, and Martina Řezáčová. "Apoptosis and Senescence – Main Mechanisms of Accelerated Aging of Haematopoietic Cells after Irradiation." Acta Veterinaria Brno 78, no. 2 (2009): 205–17. http://dx.doi.org/10.2754/avb200978020205.
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Haematopoietic stem cell (HSC) is one of the most radiosensitive cells in organism. In mice it is characterized as lin-Sca-1+CD117+ cell. This review discusses the role of HSC subpopulations in recovery of haematopoiesis after irradiation, and molecular mechanisms of reaction of HSC to damage induced by genotoxic stress, mainly to double strand breaks (DSB) of DNA. Various proteins are accumulated on the site of break, e.g. 53BP1 and γH2AX. Repair of the damage and related signalling is executed by many proteins, such as ATM, ATR, and DNA-PK kinases, MRN complex and proteins of homologous recombination and non-homologous end joining. Repetitive irradiation by low doses of ionizing radiation causes in HSC accumulation of proteins into so-called “ionizing radiation inducing foci” (detectable by γH2AX) and decreases repair capacity of HCS. Furthermore, two possible molecular mechanisms of HSC reaction to radiationinduced DNA damage are discussed – apoptosis and senescence. While majority of differentiated haematopoietic cells, leukaemic cells, and haematopoietic progenitors die after irradiation by apoptosis, in HSC also senescence was detected. It also seems that decrease in proliferative capacity of HSC related to old age is caused by accumulation of DNA damage induced by oxygen radicals in the pool of quiescent stem cells.
34
Fomin, Marina E., Ashley I. Beyer, and Marcus O. Muench. "Human fetal liver cultures support multiple cell lineages that can engraft immunodeficient mice." Open Biology 7, no. 12 (December 2017): 170108. http://dx.doi.org/10.1098/rsob.170108.
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During prenatal development the liver is composed of multiple cell types with unique properties compared to their adult counterparts. We aimed to establish multilineage cultures of human fetal liver cells that could maintain stem cell and progenitor populations found in the developing liver. An aim of this study was to test if maturation of fetal hepatocytes in short-term cultures supported by epidermal growth factor and oncostatin M can improve their ability to engraft immunodeficient mice. Fetal liver cultures supported a mixture of albumin + cytokertin-19 + hepatoblasts, hepatocytes, cholangiocytes, CD14 ++ CD32 + liver sinusoidal endothelial cells (LSECs) and CD34 + CD133 + haematopoietic stem cells. Transplantation of cultured cells into uPA-NOG or TK-NOG mice yielded long-term engraftment of hepatocytes, abundant LSEC engraftment and multilineage haematopoiesis. Haematopoietic engraftment included reconstitution of B-, T- and NK-lymphocytes. Colonies of polarized human hepatocytes were observed surrounded by human LSECs in contact with human CD45 + blood cells in the liver sinusoids. Thus, fetal liver cultures support multiple cell lineages including LSECs and haematopoietic stem cells while also promoting the ability of fetal hepatocytes to engraft adult mouse livers. Fetal liver cultures and liver-humanized mice created from these cultures can provide useful model systems to study liver development, function and disease.
35
GUILPIN, V. O., L. NOSBISCH, R. G. TITUS, and C. J. SWARDSON-OLVER. "Infection with Leishmania major stimulates haematopoiesis in susceptible BALB/c mice and suppresses haematopoiesis in resistant CBA mice." Parasitology 126, no. 3 (March 2003): 187–94. http://dx.doi.org/10.1017/s0031182002002779.
Full textAbstract:
Cytokine responses to Leishmania infection begin very early in infection, and differ between susceptible and resistant mice. Susceptibility to chronic Leishmania infection has been associated with increased haematopoiesis. To analyse the effect that acute infection with L. major has on bone-marrow haematopoiesis in susceptible (BALB/c) and resistant (CBA) mice, we enumerated erythroid progenitors and granulocyte-monocyte progenitors 3 days after infection. We found that haematopoiesis was stimulated in BALB/c mice infected with L. major, while haematopoiesis was inhibited in CBA mice. We found that this effect could be partially explained by cytokine production: interleukin-4 was involved in stimulation of BALB/c haematopoiesis and tumour necrosis factor-α was involved in inhibition of CBA haematopoiesis. Our conclusions are that haematopoietic changes occur shortly after L. major infection, and may be related to disease outcome.
36
Lewis, L. D., S. Amin, C. I. Civin, and P. S. Lietman. "Ex vivo zidovudine (AZT) treatment of CD34+ bone marrow progenitors causes decreased steady state mitochondrial DNA (mtDNA) and increased lactate production." Human & Experimental Toxicology 23, no. 4 (April 2004): 173–85. http://dx.doi.org/10.1191/0960327104ht437oa.
Full textAbstract:
Haematopoietic suppression is one of the dose-limiting side effects of chronic zidovudine (AZT) therapy. We tested the hypothesis that AZT would reduce mitochondrial DNA (mtDNA) content in haematopoietic progenitors causing impaired haematopoiesis and mitochondrial dysfunction. We studied the effects of AZT 0 / 50 M in vitro, on normal human CD34 / haematopoietic progenitor cells cultured ex vivo for up to 12 days. The mean AZT IC50 for granulocyte (phenotype CD15 / /CD14 /) and erythroid (phenotype glycophorin / /CD45 /) cell proliferation was 2.5 M (SD9 / 0.7) and 0.023 M (SD9 / 0.005), respectively. In myeloid-rich cell cultures, the mean lactate content of the media, compared to untreated controls, increased by 86% (SD9 / 23) at 10 M AZT and in erythroid-rich cultures it increased by 134% (SD9 / 24) in the presence of 0.5 M AZT. In myeloid-rich cultures the AZT IC50 for the reduction in the mitochondrial/nuclear DNA content ratio was 5.6 M, whereas in erythroid rich cultures this AZT IC50 was B / 0.0005 M. AZT produced concentration-dependent inhibition of CD34 / progenitor proliferation into both myeloid and erythroid lineages; erythropoiesis was more sensitive than myelopoiesis. Concurrently, AZT reduced steady state mtDNA content, while increasing lactate production. These findings support the hypothesis that mtDNA is one of the intracellular targets involved in the pathogenesis of AZT-associated bone marrow progenitor cell toxicity.
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Yang, Mo, Shichao Chen, Liang Li, Hongwu Xin, Beng H. Chong, and Liuming Yang. "Analysis of a New Haematopoietic Stem/Progenitor Cells with Megakaryocyte Differentiation Potential." Blood 134, Supplement_1 (November 13, 2019): 4891. http://dx.doi.org/10.1182/blood-2019-127851.
Full textAbstract:
Thrombocytopenia is a common clinical condition and requires more effective treatments. Our previous original work confirmed that 5-HT contributes to the expansion of cord blood stem/progenitor cells (CD34+/CD41+CD61+) and haematopoietic reconstitution in NOD/SCID mice, and through 5-HT2R and Erk1/2 pathway, 5-HT remodel F-actin organization, promoting megakaryocytes to pro-platelet formation (Stem Cells, 2007; 2014). It is suggested that there is a subtype of haematopoietic stem cells (CD34+5HT2R+) with the potential to differentiate into megakaryocytes (CD41+5HT2R+). We studied the specific functions of cells through subsequent experiments, including receptor expression and signaling pathways. Results showed that: (1) The presence of 5-HT2 receptors on CD34+ and CD41+ cells; (2) 5-HT activated the PI3K/AKT pathway and the Wnt/β-catenin pathway via 5-HT2R in CD34+ and CD41+ cells, with anti-apoptotic and pro-proliferative functions; (3) These CD34+5HT2R+ differentiated CD41+5HT2R+ cells, 5-HT acted on 5-HT2R and Erk1/2 pathways, and promoted the formation of pro-platelets by F-actin reorganization; (4) CD34+5HT2R+ haematopoietic stem cells implanted in NOD/SCID mice reconstituted blood function, especially on thrombopoiesis. This study provides a more scientific basis for haematopoiesis and drug development, especially for the treatment of thrombocytopenia. Disclosures No relevant conflicts of interest to declare.
38
Cavazzana-Calvo, Marina, Chantal Lagresle-Peyrou, Emmanuelle M. Six, Capucine Picard, Frederic Rieux-Laucat, Vincent Michel, Andrea Ditadi, et al. "Human Adenylate Kinase 2 Deficiency Causes a Profound Haematopoietic Defect Associated with Sensorineural Deafness." Blood 112, no. 11 (November 16, 2008): lba—2—lba—2. http://dx.doi.org/10.1182/blood.v112.11.lba-2.lba-2.
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Abstract Human adenylate kinase 2 deficiency causes the most profound human haematopoietic defect associated with sensorineural deafness. Reticular dysgenesis (RD) is an autosomal recessive form of human severe combined immunodeficiency (SCID) characterized by an early differentiation block in the myeloid lineage and a profound impairment in lymphoid maturation associated with bilateral sensorineural deafness. The lack of polymorphonuclear neutrophils in affected newborns is responsible for the occurrence of severe infections earlier than usually observed in the other forms of SCID. Furthermore, RD associated neutropenia is characterized by the lack of responsiveness to G-CSF. We have identified bi-allelic mutations in the adenylate kinase 2 (AK2) gene is seven patients affected with RD. These mutations resulted in the absence or a strong decrease in protein expression. Restoration of AK2 expression in the bone marrow cells of RD patients overcomes the neutrophil differentiation arrest, underlying its specific requirement in the development of a restricted set of haematopoietic lineages. Lastly, we established that AK2 is specifically expressed in the stria vascularis region of the inner ear. The function of this gene in the differentiation of a given set of cell lineages is rapidly in progress, showing that studies of primary immunodeficiencies continue to provide key information on human lympho-haematopoietic development. Moreover the AK2 enzyme seems a key molecule in different biological systems such as the lympho-haematopoiesis and the brain development.
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Gerber, Julia P., Jenny Russ, Vijay Chandrasekar, Nina Offermann, Hang-Mao Lee, Sarah Spear, Nicola Guzzi, et al. "Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation." Nature Cell Biology 23, no. 12 (December 2021): 1224–39. http://dx.doi.org/10.1038/s41556-021-00774-y.
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AbstractDefective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.
40
Lo Celso, Cristina, Edwin D. Hawkins, Delfim Duarte, Olufolake Akinduro, Reema A. Khorshed, Diana Passaro, Malgorzata Nowicka, et al. "Intravital Microscopy Reveals Fundamental Differences in the Interaction of Stem Cells and T Acute Lymphoblastic Leukaemia with the Bone Marrow Microenvironment." Blood 128, no. 22 (December 2, 2016): 5199. http://dx.doi.org/10.1182/blood.v128.22.5199.5199.
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Abstract Haematopoiesis is the complex developmental process maintaining the turnover of all blood cell lineages, i.e. erythrocytes, immune (white) cells and platelets. It takes place primarily in the bone marrow, where it critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). This is regulated by complex interactions between stem cells and the bone marrow microenvironment, and it was suggested to change in settings involving stress. Indeed, using intravital microscopy, we previously showed that HSCs injected in irradiated recipients steadily engage with endosteal niches. Moreover, if phenotypically identical HSCs are harvested from mice harbouring a natural infection, such as that caused by T.spiralis, they show a unique 'stop and go' migratory behaviour, engage larger niches, yet remain in the proximity of osteoblastic cells. Based on these and other studies, it has been hypothesised that also malignant haematopoietic cells rely on interactions with specific bone marrow microenvironments to grow, and especially to develop chemoresistance. To investigate this further, we performed longitudinal imaging of mice injected with murine and human T acute lymphoblastic leukaemia (T-ALL) cells over the course of hours or days, including during response to multiple chemotherapy treatments. Strikingly, we observed a very different behaviour from that of HSCs, with T-ALL cells showing a highly migratory behaviour throughout all stages of disease, from initial bone marrow infiltration to response to chemotherapy. Interestingly, in untreated mice and in patients trephine biopsies we observed rapid loss of osteoblastic cells by apoptosis, an event that likely contributes to the dramatic loss of healthy haematopoiesis observed in mice and patients. Together, these finds indicate that novel therapeutic strategies should target the ability of T-ALL cells to entertain short-lived and promiscuous interactions with any neighbouring cells, and aim to strengthen the bone marrow microenvironment to improve support for residual healthy haematopoiesis. Disclosures Harrison: AbbVie: Research Funding; Janssen Cilag: Research Funding, Speakers Bureau. Quach:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.
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Kawa, Miłosz Piotr, Katarzyna Grymuła, Edyta Paczkowska, Magdalena Baśkiewicz-Masiuk, Elżbieta Dąbkowska, Monika Koziołek, Maciej Tarnowski, et al. "Clinical relevance of thyroid dysfunction in human haematopoiesis: biochemical and molecular studies." European Journal of Endocrinology 162, no. 2 (February 2010): 295–305. http://dx.doi.org/10.1530/eje-09-0875.
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ObjectiveAbnormalities in haematological parameters have been noted in patients with thyroid diseases. Nevertheless, the exact mechanism of thyroid hormones' (THs) action on human haematopoiesis is still not entirely clear.DesignThe influence of THs through TH receptors (TRα-1 and TRβ-1) on haematopoiesis in patients with hypo- and hyperthyroidism was analysed.MethodsTR gene expression at the mRNA and protein levels in human CD34+-enriched haematopoietic progenitor cells (HPCs) obtained from the peripheral blood of patients with thyroid disorders and healthy volunteers was analysed. The cell populations were also investigated for clonogenic growth of granulocyte macrophage-colony forming units and erythrocyte-burst forming units (BFU-E). The level of apoptosis was determined by annexin V/propidium iodide staining and quantitative RT-PCR.ResultsThe studies revealed that hypo- and hyperthyroidism modify TR gene expression in HPCs in vivo. TH deficiency resulted in a decrease in total blood counts and clonogenic potential of BFU-E. In contrast, hyperthyroid patients presented increased clonogenic growth and BFU-E number and significantly higher expressions of cell cycle-regulating genes such as those for PCNA and cyclin D1. Finally, an increase in the frequency of apoptotic CD34+-enriched HPCs in hypo- and hyperthyroidism with a modulation of apoptosis-related genes was detected.ConclusionsThe following conclusions were derived: i) TR expression in human haematopoietic cells depends on TH status, ii) both hypo- and hyperthyroidism significantly influence clonogenicity and induce apoptosis in CD34+-enriched HPCs and iii) the molecular mechanism by which THs influence haematopoiesis might provide a basis for designing novel therapeutic interventions in thyroid diseases.
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Dragoljevic, Dragana, Marit Westerterp, Camilla Bertuzzo Veiga, Prabhakara Nagareddy, and Andrew J. Murphy. "Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis." Clinical Science 132, no. 17 (September 5, 2018): 1889–99. http://dx.doi.org/10.1042/cs20180111.
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Cardiovascular (CV) diseases (CVD) are primarily caused by atherosclerotic vascular disease. Atherogenesis is mainly driven by recruitment of leucocytes to the arterial wall, where macrophages contribute to both lipid retention as well as the inflammatory milieu within the vessel wall. Consequently, diseases which present with an enhanced abundance of circulating leucocytes, particularly monocytes, have also been documented to accelerate CVD. A host of metabolic and inflammatory diseases, such as obesity, diabetes, hypercholesteraemia, and rheumatoid arthritis (RA), have been shown to alter myelopoiesis to exacerbate atherosclerosis. Genetic evidence has emerged in humans with the discovery of clonal haematopoiesis of indeterminate potential (CHIP), resulting in a disordered haematopoietic system linked to accelerated atherogenesis. CHIP, caused by somatic mutations in haematopoietic stem and progenitor cells (HSPCs), consequently provide a proliferative advantage over native HSPCs and, in the case of Tet2 loss of function mutation, gives rise to inflammatory plaque macrophages (i.e. enhanced interleukin (IL)-1β production). Together with the recent findings of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial that revealed blocking IL-1β using Canakinumab reduced CV events, these studies collectively have highlighted a pivotal role of IL-1β signalling in a population of people with atherosclerotic CVD. This review will explore how haematopoiesis is altered by risk-factors and inflammatory disorders that promote CVD. Further, we will discuss some of the recent genetic evidence of disordered haematopoiesis in relation to CVD though the association with CHIP and suggest that future studies should explore what initiates HSPC mutations, as well as how current anti-inflammatory agents affect CHIP-driven atherosclerosis.
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Silberstein, Lev, Maria Jose Sanchez, Merav Socolovsky, Gary J. Hoffman, Sandie Piltz, Mark Bowen, Anthony R. Green, and Berthold Gottgens. "An SCL +19 Core Enhancer Targets Three Mesoderm-Derived Cell Lineages - Blood, Endothelium and Smooth Muscle." Blood 104, no. 11 (November 16, 2004): 4200. http://dx.doi.org/10.1182/blood.v104.11.4200.4200.
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Abstract The stem cell leukaemia (SCL) gene encodes a basic helix-loop-helix transcription factor with a critical role in normal haematopoiesis and angiogenesis. The SCL gene is normally expressed in haematopoietic stem cells, mast cells, megakaryocytes, endothelium and smooth muscle. Aberrant expression of the SCL gene leads to T-cell acute lymphoblastic leukaemia, whereas SCL−/− mice die due to the absence of haematopoiesis. Hence, temporal and spatial regulation of SCL expression is essential. Our laboratory has previously characterised a 5.5 kb enhancer located 3′ of the SCL transcription start site, which is capable of targeting expression of b-galactozidase (LacZ) reporter gene to haematopoietic stem cells in the foetal liver and the bone marrow, as well as embryonic endothelium. Subsequent experiments showed that a 641-base pair core enhancer gave an identical pattern of lacZ expression in the embryo. However, it was unclear if the same element (later referred to as +19 core enhancer) was capable of maintaining reporter gene expression into the adulthood, since no lacZ activity was observed in postnatal mice. Using a transgenic construct containing a eukaryotic reporter gene, human placental alkaline phosphatase, we show that in the haematopoietic system, the +19 core enhancer is sufficient to target foetal liver and bone marrow HSCs, as well as mast cells and megakaryocytes. In the erythroid lineage, the enhancer is active only during the earlier stages of erythropoiesis, despite high level of SCL expression throughout erythroblast maturation, suggesting that an additional element is likely to be required to maintain SCL expression. The enhancer also targets embryonic and adult endothelium, together with vascular and visceral smooth muscle. Taken together, our results demonstrate that the 641-bp +19 core enhancer is sufficient to integrate signals upstream of SCL in blood, endothelium and smooth muscle. Our data also suggest that developmental relationship between these three mesoderm-derived lineages could be defined through a common transcriptional environment, and indicate that SCL may play a wider role in mesodermal development than previously thought.
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Kato, Itaru, Akira Niwa, Katsutsugu Umeda, Mamoru Ito, Toshio Heike, and Tatsutoshi Nakahata. "NOD/SCID/γcnull mice provide a Unique Model to Investigate Childhood Haematopoietic Malignancies." Blood 112, no. 11 (November 16, 2008): 3963. http://dx.doi.org/10.1182/blood.v112.11.3963.3963.
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Abstract Remarkable improvements in the outcome for childhood haematopoietic malignancies have been made during the past few decades. However, haematopoietic malignancies are the most common pediatric malignancy, and outcome after relapse is generally poor. Recent reports suggest that at least some cases of human leukemia and cancer are arranged in a hierarchical fashion and maintained by rare “tumor-propagating cells”. However, whether the malignant clone arises from such a leukemic stem cell fraction has not been clarified in most haematopoietic malignancies other than acute myelogenous leukemia (AML). Establishment of an assay capable of generating of childhood haematopoietic malignancies from patient oriented blast cells will provide new insight into the haematopoietic malignancies biology and the mechanism of the development of haematopoietic malignancies in vivo. The recently described highly immunodeficient NOD/SCID/gamma null (NOG) mice provide a number of advantages. This strain, with life expectancy more than 90 weeks, is more robust than strains such as NOD/SCID and support generation of haematopoietic malignancies from transplanted human blast cells. In the present study, childhood haematopoietic malignancies cells, such as acute lymphoblastic leukemia(ALL; n=7), AML (n=4), juvenile myelomonocytic leukemia(JMML; n=1), Lymphoma(n=1), and Transient Myeloproliferative Disorder(n=1), are transplanted into 2.4Gy irradiated or non-irradiated NOG mice. The transplanted mice have splenomegaly, hepatomegaly, nephromegaly and testicular enlargement and developed haematopoietic malignancies which is the same flow cytometric immunophenotype and pathological pattern of the patient from 4 weeks after intravenous injection of 5×102-1×108 blast cells. The transplanted mice can live as long as 24 weeks after transplantation with more than 95% blasts in the bone marrow. The blast cells harvested from the bone marrow and the spleen generated the haematopoietic malignancies in tertiary transplantation especially in ALL. We report here examination results of reconstituted childhood haematopoietic malignancies in NOD/SCID/gamma null mice after the transplantation of patient oriented blast cells.
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Traynor, Breege. "Haematopoietic growth factors." Nursing Standard 5, no. 18 (January 23, 1991): 32–34. http://dx.doi.org/10.7748/ns.5.18.32.s32.
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Weitzman, Jonathan B. "Haematopoietic stem cells." Genome Biology 4 (2003): spotlight—20030122–01. http://dx.doi.org/10.1186/gb-spotlight-20030122-01.
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STRASSER, A. "Haematopoietic cell apoptosis." Current Opinion in Immunology 19, no. 5 (October 2007): 485–87. http://dx.doi.org/10.1016/j.coi.2007.07.014.
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Bonnet, Dominique. "Haematopoietic stem cells." Journal of Pathology 197, no. 4 (2002): 430–40. http://dx.doi.org/10.1002/path.1153.
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Gruszka, Alicja, Debora Valli, Cecilia Restelli, and Myriam Alcalay. "Adhesion Deregulation in Acute Myeloid Leukaemia." Cells 8, no. 1 (January 17, 2019): 66. http://dx.doi.org/10.3390/cells8010066.
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Cell adhesion is a process through which cells interact with and attach to neighboring cells or matrix using specialized surface cell adhesion molecules (AMs). Adhesion plays an important role in normal haematopoiesis and in acute myeloid leukaemia (AML). AML blasts express many of the AMs identified on normal haematopoietic precursors. Differential expression of AMs between normal haematopoietic cells and leukaemic blasts has been documented to a variable extent, likely reflecting the heterogeneity of the disease. AMs govern a variety of processes within the bone marrow (BM), such as migration, homing, and quiescence. AML blasts home to the BM, as the AM-mediated interaction with the niche protects them from chemotherapeutic agents. On the contrary, they detach from the niches and move from the BM into the peripheral blood to colonize other sites, i.e., the spleen and liver, possibly in a process that is reminiscent of epithelial-to-mesenchymal-transition in metastatic solid cancers. The expression of AMs has a prognostic impact and there are ongoing efforts to therapeutically target adhesion in the fight against leukaemia.
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Al-Chalabi, Ali Saeed, and Walaa Aladdin Mustafa. "Study of Bone Marrow Cells During First Three Months Old Rats." Kufa Journal For Veterinary Medical Sciences 13, no. 2 (December 31, 2022): 13–23. http://dx.doi.org/10.36326/kjvs/2022/v13i23883.
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Haematopoiesis is very complicated process of formation, development, and differentiation of bone marrow cells and its evaluation is very valuable diagnostic tool for the veterinary practitioner. So, the aim of study is to evaluate the healthy bone marrow cytology during first three months old. Ninety pups were involved throughout the study according to study design. Growing pups were kept with their moms till the weaning day, then divided into three main groups (1, 2, and 3 months old). After reaching the appropriate study age, bone marrow samples were obtained, and bone marrow smears were carried out and stained with MGGS. The results revealed presence of all types of haematopoietic cells and there are increase in different erythroid progenitor and myeloid progenitor with the age progress. Furthermore, the smears showed different cell line production with different differentiation stages of both erythroid and myeloid cells. In conclusion the bone marrow cells differentiation and proliferation are related to age progress independently. Haematopoietic cells differentiation and proliferation are regulated by bone marrow microenvironment. Myeloid cells are directly related to age progress.