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Zhongguo Shi Yan Xue Ye Xue Za Zhi Apr 2016To investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics...
OBJECTIVE
To investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.
METHODS
The immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.
RESULTS
There was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.
Topics: Antigens, CD; Cell Count; Flow Cytometry; Granulocyte Precursor Cells; HLA-DR Antigens; Humans; Immunophenotyping; Leukemia, Promyelocytic, Acute; Leukocyte Common Antigens; Prognosis
PubMed: 27150985
DOI: 10.7534/j.issn.1009-2137.2016.02.003 -
Blood May 2021
Topics: Adolescent; Azure Stains; Blast Crisis; Bone Marrow; Cytoplasmic Granules; Diabetes Mellitus, Type 1; Diagnosis, Differential; Fusion Proteins, bcr-abl; Granulocyte Precursor Cells; HLA-DR Antigens; Humans; Interleukin-3 Receptor alpha Subunit; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocytosis; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Staining and Labeling; Thrombocytopenia
PubMed: 34014290
DOI: 10.1182/blood.2021011420 -
Cell Death & Disease Jul 2021Mutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is...
Mutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.
Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cells, Cultured; Female; Gene Expression Regulation, Leukemic; Granulocyte Precursor Cells; Homeodomain Proteins; Leukemia, Monocytic, Acute; Mice, Inbred C57BL; Mutation; Neutrophils; Up-Regulation; Mice
PubMed: 34226527
DOI: 10.1038/s41419-021-03948-6 -
Cell Cycle (Georgetown, Tex.) Dec 2006Inactivation of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1) (CDKN1; hereafter p21) has previously been implicated in the induction of numerical centrosome...
Inactivation of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1) (CDKN1; hereafter p21) has previously been implicated in the induction of numerical centrosome alterations. It is unclear, however, whether p21 deficiency deregulates the centrosome duplication cycle itself or causes an accumulation of centrosomes due to cell division failure and/or polyploidization. Using a novel marker for maternal centrioles, Cep170, we show here that knock-down of p21 protein expression in murine myeloblasts can stimulate excessive centriole numbers in the presence of only one mature centriole. These results indicate that p21 deficiency can trigger a bona fide overduplication of centrioles and that aberrant centrosome numbers cannot solely be explained by polyploidization as suggested by previous studies. Our findings underscore that impaired p21 expression may function as a driving force for chromosomal instability and highlight the importance of markers for maternal centrioles such as Cep170 to elucidate the pathogenesis of numerical centriole aberrations in tumor cells.
Topics: Animals; Centrioles; Cyclin-Dependent Kinase Inhibitor p21; Granulocyte Precursor Cells; Mice; RNA, Small Interfering
PubMed: 17172866
DOI: 10.4161/cc.5.24.3567 -
Blood Nov 2011
Topics: Benzylamines; Cyclams; Female; Granulocyte Precursor Cells; Heterocyclic Compounds; Humans; Immunologic Deficiency Syndromes; Lymphopenia; Male; Primary Immunodeficiency Diseases; Warts
PubMed: 22053172
DOI: 10.1182/blood-2011-08-375162 -
Leukemia Aug 2019
Topics: AC133 Antigen; Antigens, CD19; Granulocyte Precursor Cells; Humans; Immunotherapy; Leukemia, Biphenotypic, Acute; Receptors, Chimeric Antigen
PubMed: 30778134
DOI: 10.1038/s41375-019-0418-8 -
Bioorganic & Medicinal Chemistry Jul 2015A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of...
A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.28±0.07μM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid moiety in the molecules.
Topics: Anti-HIV Agents; Binding Sites; Cell Line; Drug Design; Granulocyte Precursor Cells; HIV Reverse Transcriptase; HIV-1; Humans; Models, Molecular; Molecular Docking Simulation; Pyrimidines; Quinolones; Reverse Transcriptase Inhibitors; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; Virus Latency
PubMed: 25907370
DOI: 10.1016/j.bmc.2015.03.037 -
Journal of Immunology (Baltimore, Md. :... Jul 2023The mechanism of the development of granulocyte progenitor cells into neutrophils under steady-state and pathological conditions remains unclear. In this study, our...
The mechanism of the development of granulocyte progenitor cells into neutrophils under steady-state and pathological conditions remains unclear. In this study, our results showed that with the development of neutrophils from hematopoietic stem cells to mature neutrophils, the expression level of the Hippo kinase MST1 gradually increased. Mst1-specific deficiency in myeloid cells caused neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte-macrophage progenitors under steady-state conditions and during Listeria monocytogenes infection. Mechanistically, mTOR and HIF1α signaling are required for regulating the balance between glycolysis and succinate dehydrogenase-mediated oxidative phosphorylation, which is crucial for Mst1-/--induced proliferation of granulocyte-monocyte progenitors, lineage-decision factor C/EBPα expression, and granulopoiesis. HIF1α directly regulated C/EBPα promoter activities. Blocking mTOR and HIF1α or adjusting the balance between glycolysis and succinate dehydrogenase-mediated oxidative phosphorylation reversed the granulopoiesis induced by Mst1-/- under steady-state conditions or infection in mice. Thus, our findings identify a previously unrecognized interplay between Hippo kinase MST1 signaling and mTOR-HIF1α metabolic reprogramming in granulocyte progenitor cells that underlies granulopoiesis.
Topics: Animals; Mice; Cell Differentiation; Granulocyte Precursor Cells; Homeostasis; Succinate Dehydrogenase; TOR Serine-Threonine Kinases
PubMed: 37184367
DOI: 10.4049/jimmunol.2200615 -
Journal of Immunology (Baltimore, Md. :... Mar 2022Protein tyrosine phosphatase (PTPase) is critically involved in the regulation of hematopoietic stem cell development and differentiation. Roles of novel isolated...
Protein tyrosine phosphatase (PTPase) is critically involved in the regulation of hematopoietic stem cell development and differentiation. Roles of novel isolated receptor PTPase PTPRO from bone marrow hematopoietic stem cells in granulopoiesis have not been investigated. PTPRO expression is correlated with granulocytic differentiation, and mice developed neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors under steady-state and potentiated innate immune responses against infection. Mechanistically, mTOR and HIF1α signaling engaged glucose metabolism and initiated a transcriptional program involving the lineage decision factor C/EBPα, which is critically required for the PTPRO deficiency-directed granulopoiesis. Genetic ablation of mTOR or HIF1α or perturbation of glucose metabolism suppresses progenitor expansion, neutrophilia, and higher glycolytic activities by In addition, upregulated HIF1α regulates the lineage decision factor α promoter activities. Thus, our findings identify a previously unrecognized interplay between receptor PTPase PTPRO signaling and mTOR-HIF1α metabolic reprogramming in progenitor cells of granulocytes that underlies granulopoiesis.
Topics: Animals; Glucose; Granulocyte Precursor Cells; Granulocytes; Mice; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 3; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 35246496
DOI: 10.4049/jimmunol.2100878 -
Nature Communications Sep 2015Staphylococcus aureus subverts host defences by producing a collection of virulence factors including bi-component pore-forming leukotoxins. Despite extensive sequence...
Staphylococcus aureus subverts host defences by producing a collection of virulence factors including bi-component pore-forming leukotoxins. Despite extensive sequence conservation, each leukotoxin has unique properties, including disparate cellular receptors and species specificities. How these toxins collectively influence S. aureus pathogenesis is unknown. Here we demonstrate that the leukotoxins LukSF-PV and LukED antagonize each other's cytolytic activities on leukocytes and erythrocytes by forming inactive hybrid complexes. Remarkably, LukSF-PV inhibition of LukED haemolytic activity on both human and murine erythrocytes prevents the release of nutrients required for in vitro bacterial growth. Using in vivo murine models of infection, we show that LukSF-PV negatively influences S. aureus virulence and colonization by inhibiting LukED. Thus, while S. aureus leukotoxins can certainly injure immune cells, the discovery of leukotoxin antagonism suggests that they may also play a role in reducing S. aureus virulence and maintaining infection without killing the host.
Topics: Animals; Bacterial Proteins; Bacterial Toxins; Cell Death; Cell Line; Erythrocytes; Exotoxins; Granulocyte Precursor Cells; Humans; Leukocidins; Mice; Neutrophils; Staphylococcal Infections; Staphylococcus aureus; Virulence; Virulence Factors
PubMed: 26330208
DOI: 10.1038/ncomms9125