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Neuroimmunomodulation 2008Aging is associated with a decline in immune function (immunosenescence), a condition known to correlate with increased incidence of cancer as well as infectious and... (Review)
Review
Aging is associated with a decline in immune function (immunosenescence), a condition known to correlate with increased incidence of cancer as well as infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. Circulating melatonin decreases with age, and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes and macrophages. It also stimulates the production of natural killer cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from natural killer cells and T helper lymphocytes are enhanced by melatonin. Melatonin has the potential therapeutic value to enhance immune function in aged individuals.
Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Aging; Circadian Rhythm; Cytokines; Granulocyte Precursor Cells; Humans; Immune System; Immunity, Innate; Immunocompetence; Killer Cells, Natural; Melatonin; Neuroimmunomodulation; Pineal Gland; Receptors, Melatonin; Secretory Rate; Sleep; Superior Cervical Ganglion; Sympathetic Fibers, Postganglionic; T-Lymphocyte Subsets
PubMed: 19047804
DOI: 10.1159/000156470 -
Hematological Oncology Dec 2008It has long been considered that flow cytometry (FCM) has little role in clinical practice in the diagnosis of myelodysplastic syndromes (MDS). However, recent advances... (Review)
Review
It has long been considered that flow cytometry (FCM) has little role in clinical practice in the diagnosis of myelodysplastic syndromes (MDS). However, recent advances in the analytical method and knowledge of MDS FCM are changing this stereotype. This paper reviews the concept and current status of FCM in the diagnosis of low-grade MDS. The diagnosis of low-grade MDS in the absence of ringed sideroblasts and chromosomal aberration is not always straightforward, and a report from a recent international working conference has proposed FCM as an adjunctive diagnostic test for such cases. Currently, only a limited number of laboratories are applying FCM to the diagnosis of MDS. Furthermore, standard analytical methods in FCM for MDS have not been established, and no single FCM parameter is sufficiently sensitive and specific to make the diagnosis of MDS. To establish MDS FCM as a widely accepted, dependable diagnostic tool, prospective studies should increase flow parameters that can be analysed reproducibly and determine their sensitivity and specificity, either alone or in combination. CD34+ cell-related parameters that are applicable for diagnosing low-grade MDS in many laboratories are introduced here.
Topics: Antigens, CD34; Flow Cytometry; Forecasting; Granulocyte Precursor Cells; Humans; Leukocyte Common Antigens; Myelodysplastic Syndromes; Pattern Recognition, Visual; Precursor Cells, B-Lymphoid; Reproducibility of Results; Sensitivity and Specificity
PubMed: 18412289
DOI: 10.1002/hon.857 -
Best Practice & Research. Clinical... Mar 2014Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) associated with peculiar biologic and clinical features and requiring specific... (Review)
Review
Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) associated with peculiar biologic and clinical features and requiring specific management. At the genetic level, APL is featured by a unique chromosome translocation t(15;17) which results in the PML-RARα gene fusion and chimeric protein. APL is the first example of differentiation therapy targeted to a defined genetic target i.e. PML-RARα. PML-RARα behaves as an altered retinoic acid receptor with an ability of transmitting oncogenic signaling leading to accumulation of undifferentiated promyelocytes. All-trans-retinoic acid (ATRA) induces disease remission in APL patients by triggering terminal differentiation of leukemic promyelocytes. More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARα oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Elucidating the oncogenic signaling of PML-RARα through various transcription factors and the study of APL mouse models have greatly helped to understand the molecular pathogenesis of APL. However, the precise molecular mechanism by which t(15;17) is formed and initiates leukemia remains unknown. While transforming oncogenic potential of PML-RARα has been described extensively, the mechanistic events important for the formation of t(15;17) have been taken from the model of Therapy-related APL (t-APL).
Topics: Animals; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Cell Differentiation; Cell Transformation, Neoplastic; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Clinical Trials as Topic; DNA End-Joining Repair; Disease Models, Animal; Drug Synergism; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Mice; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasms, Second Primary; Neoplastic Stem Cells; Oncogene Proteins, Fusion; Oxides; Signal Transduction; Topoisomerase II Inhibitors; Translocation, Genetic; Tretinoin
PubMed: 24907012
DOI: 10.1016/j.beha.2014.04.006 -
Oncology (Williston Park, N.Y.) Jul 2012The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the... (Review)
Review
The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the most curable subtype of acute myeloid leukemia (AML). Patients who do not survive generally succumb within the first 30 days after presentation or diagnosis, often from intracranial or pulmonary hemorrhage caused by the characteristic coagulopathy associated with this disease. For the majority of patients who avoid hemorrhagic complications, the goals of decreasing the side effects of diagnosis and treatment-including pain, inpatient hospital days, and late sequelae of cytotoxic chemotherapy-have emerged as paramount. Here, we discuss novel and provocative observations regarding diagnostic and treatment strategies for APL that are likely to emerge as standards of care in the next 5 years, and that may improve the rate of early hemorrhagic death and decrease diagnosis- and treatment-related morbidity.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Arsenic Trioxide; Arsenicals; Biopsy, Fine-Needle; Bone Marrow; Clinical Trials as Topic; Dexamethasone; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Oxides; Practice Guidelines as Topic; Prognosis; Pulmonary Edema; Remission Induction; Respiratory Insufficiency; Tretinoin
PubMed: 22888564
DOI: No ID Found -
Molecules (Basel, Switzerland) Sep 2017Glucosinolates (GSLs) are widely known secondary metabolites that have anticarcinogenic and antioxidative activities in humans and defense roles in plants of the... (Review)
Review
Glucosinolates (GSLs) are widely known secondary metabolites that have anticarcinogenic and antioxidative activities in humans and defense roles in plants of the Brassicaceae family. Some R2R3-type MYB (myeloblastosis) transcription factors (TFs) control GSL biosynthesis in . However, studies on the MYB TFs involved in GSL biosynthesis in species are limited because of the complexity of the genome, which includes an increased number of paralog genes as a result of genome duplication. The recent completion of the genome sequencing of the species permits the identification of MYB TFs involved in GSL biosynthesis by comparative genome analysis with . In this review, we describe various findings on the regulation of GSL biosynthesis in Brassicaceae. Furthermore, we identify 63 orthologous copies corresponding to five MYB TFs from , except MYB76 in species. Fifty-five MYB TFs from the species possess a conserved amino acid sequence in their R2R3 MYB DNA-binding domain, and share close evolutionary relationships. Our analysis will provide useful information on the 55 MYB TFs involved in the regulation of GSL biosynthesis in species, which have a polyploid genome.
Topics: Amino Acid Sequence; Arabidopsis; Binding Sites; Brassicaceae; Conserved Sequence; Gene Expression Regulation, Plant; Glucosinolates; Granulocyte Precursor Cells; Phylogeny; Plant Proteins; Polyploidy; Proto-Oncogene Proteins c-myb; Secondary Metabolism
PubMed: 28906468
DOI: 10.3390/molecules22091549 -
Leukemia Nov 2006Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained...
Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained from 16 patients were compared to eight samples of CD34+-derived normal promyelocytes. Malignant promyelocytes showed widespread changes in transcription in comparison to their normal counterpart and 1020 differentially expressed genes were identified. Discriminating genes include transcriptional regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and HGF) was also confirmed at protein level. Interestingly, a trend toward a transcriptional repression of genes involved in different DNA repair pathways was found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new set of nine APLs. Our results suggest that both inefficient base excision repair and recombinational repair might play a role in APLs development. To investigate the expression pathways underlying the development of APL occurring as a second malignancy (sAPL), we included in our study eight cases of sAPL. Although both secondary and de novo APL were characterized by a strong homogeneity in expression profiling, we identified a small set of differentially expressed genes that discriminate sAPL from de novo cases.
Topics: Adult; Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Cluster Analysis; DNA Repair; Female; Flow Cytometry; Gene Expression Regulation, Leukemic; Granulocyte Precursor Cells; Humans; Hyaluronan Receptors; Immunophenotyping; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Sialic Acid Binding Ig-like Lectin 3; Transcription, Genetic; fms-Like Tyrosine Kinase 3
PubMed: 16990782
DOI: 10.1038/sj.leu.2404376 -
Blood Mar 2004Several lines of investigation suggest that granulocyte colony-stimulating factor (G-CSF) augments all-trans retinoic acid (ATRA)-induced neutrophil differentiation in...
Several lines of investigation suggest that granulocyte colony-stimulating factor (G-CSF) augments all-trans retinoic acid (ATRA)-induced neutrophil differentiation in acute promyelocytic leukemia (APL). We sought to characterize the relationship between G-CSF- and ATRA-mediated neutrophil differentiation. We established a G-CSF receptor-transduced promyelocytic cell line, EPRO-Gr, derived from the granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent EPRO cell line harboring a dominant-negative retinoic acid receptor alpha (RARalpha). In EPRO-Gr, neutrophil differentiation occurs either in GM-CSF upon addition of ATRA or upon induction with G-CSF alone. Transient transfection of EPRO-Gr cells with a RARE-containing reporter plasmid demonstrates increased activity in the presence of ATRA, but not G-CSF, while STAT3 phosphorylation occurs only in response to G-CSF. This suggests that ATRA-mediated differentiation of EPRO-Gr cells occurs via a RARE-dependent, STAT3-independent pathway, while G-CSF-mediated differentiation occurs via a RARE-independent, STAT3-dependent pathway. ATRA and G-CSF thus regulate differentiation by divergent pathways. We characterized these pathways in the APL cell line, NB4. ATRA induction of NB4 cells resulted in morphologic differentiation and up-regulation of C/EBPepsilon and G-CSFR, but not in STAT3 phosphorylation. The addition of G-CSF with ATRA during NB4 induction resulted in STAT3 phosphorylation but did not enhance differentiation. These results may elucidate how G-CSF and ATRA affect the differentiation of primary and ATRA-resistant APL cells.
Topics: Animals; Blotting, Northern; Blotting, Western; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Survival; Chromatin; DNA-Binding Proteins; Genes, Reporter; Granulocyte Colony-Stimulating Factor; Granulocyte Precursor Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Luciferases; Mice; Neutrophils; Phosphorylation; Plasmids; Precipitin Tests; Receptors, Retinoic Acid; Response Elements; Retinoic Acid Receptor alpha; Retroviridae; STAT3 Transcription Factor; Signal Transduction; Time Factors; Trans-Activators; Transfection; Up-Regulation
PubMed: 14604978
DOI: 10.1182/blood-2002-10-3247 -
Best Practice & Research. Clinical... Mar 2014Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the... (Review)
Review
Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications remain the major causes of early deaths. In this chapter, the known causes of abnormalities in haemostatic function, namely the coagulopathy and changes in the fibrinolytic system, will be reviewed. Major risk factors for these complications are identified. Current available measures for correction of the coagulopathy and their effectiveness are critically examined. Unless the coagulopathy can be effectively controlled, bleeding complications will remain an obstacle to achieving a cure for this disease. The issues that need to be addressed in next phase of investigations are also discussed.
Topics: Annexin A2; Anticoagulants; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Blood Coagulation Disorders; Blood Coagulation Tests; Carboxypeptidase B2; Disseminated Intravascular Coagulation; Fibrinolysis; Forecasting; Granulocyte Precursor Cells; Hemorrhagic Disorders; Humans; Leukemia, Promyelocytic, Acute; Oxides; Recombinant Proteins; Risk Factors; S100 Proteins; Thrombomodulin; Thrombophilia; Thromboplastin; Tretinoin; Urokinase-Type Plasminogen Activator
PubMed: 24907013
DOI: 10.1016/j.beha.2014.04.005 -
Journal of Bronchology & Interventional... Oct 2020
Topics: Aged; Bone Marrow; Bronchi; Bronchoscopy; Cough; Disease Progression; Fatal Outcome; Female; Granulocyte Precursor Cells; Humans; Neoplasm Recurrence, Local; Palliative Care; Sarcoma, Myeloid; Tomography, X-Ray Computed; Trachea
PubMed: 32604321
DOI: 10.1097/LBR.0000000000000693 -
Cytometry. Part B, Clinical Cytometry 2011The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This... (Review)
Review
The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and determining individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts). Therefore, there is clearly a need to refine the accuracy to detect marrow dysplasia. Flow cytometry (FCM) immunophenotyping has been proposed as a tool to improve the evaluation of marrow dysplasia. Rationale for the application of FCM in the diagnostic work up of MDS is that immunophenotyping is an accurate method for quantitative and qualitative evaluation of hematopoietic cells and that MDS have been found to have abnormal expression of several cellular antigens. To become clinically applicable, FCM analysis should be based on parameters with sufficient specificity and sensitivity, data should be reproducible between different operators and the results should be easily understood by clinicians. In this report, we reviewed the most relevant progresses in detection of marrow dysplasia by FCM in MDS as defined by WHO criteria.
Topics: Antigens, CD; Bone Marrow; Erythroid Cells; Flow Cytometry; Granulocyte Precursor Cells; Humans; Immunophenotyping; Myelodysplastic Syndromes; Phenotype; World Health Organization
PubMed: 21674774
DOI: 10.1002/cyto.b.20607