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Leukemia & Lymphoma Sep 2002Normal promyelocytes express CD45RO, while acute promyelocytic leukemia (APL) blasts express CD45RA, both isoforms of common leukocyte antigen with mutually exclusive...
Normal promyelocytes express CD45RO, while acute promyelocytic leukemia (APL) blasts express CD45RA, both isoforms of common leukocyte antigen with mutually exclusive expression. Here we report a patient with accumulation of promyelocytes in the bone marrow and the diagnostic strategy is described along with the ability to quickly discriminate between normal and abnormal cells using the flow cytometric detection of expression of RA/RO isoforms of CD45.
Topics: Bone Marrow Cells; Female; Flow Cytometry; Granulocyte Precursor Cells; Humans; Immunophenotyping; Leukemia, Promyelocytic, Acute; Leukocyte Common Antigens; Middle Aged; Protein Isoforms
PubMed: 12685839
DOI: 10.1080/1042819021000006538 -
Medizinische Klinik (Munich, Germany :... Apr 2007The continuously growing knowledge about criteria important for biology, pathogenesis, prognosis and treatment of acute myeloid leukemia (AML) necessitates a broad... (Review)
Review
DIAGNOSTICS
The continuously growing knowledge about criteria important for biology, pathogenesis, prognosis and treatment of acute myeloid leukemia (AML) necessitates a broad spectrum of diagnostic methods for first diagnosis and for the further course of the disease. Relevant diagnostic techniques (cytomorphology with cytochemistry, immunophenotyping, cytogenetics and molecular genetics, DNA array) are described - with a focus on their mode of operation as well on their clinical significance. Due to the high clinical relevance and growing complexity, AML diagnostics should be performed in specialized laboratories.
CLASSIFICATION
Compared to the FAB classification which is based primarily on morphological criteria, the classification recommended in 2001 by the WHO additionally takes cytogenetics, molecular genetics and further clinical factors into consideration. Both classifications are described.
PROGNOSTIC CRITERIA
A wide range of prognostic criteria of AML is discussed on the basis of currently available clinical data. The most important criteria are the karyotype of the leukemic clone and the patient's age.
Topics: Age Factors; Bone Marrow; Chromosome Aberrations; DNA Mutational Analysis; Granulocyte Precursor Cells; Humans; Inclusion Bodies; Karyotyping; Leukemia, Myeloid, Acute; Prognosis
PubMed: 17426933
DOI: 10.1007/s00063-007-1036-1 -
Indian Journal of Pathology &... Apr 2024
Topics: Humans; Bone Marrow; Granulocyte Precursor Cells; Histocytochemistry; Inclusion Bodies; Microscopy
PubMed: 38391365
DOI: 10.4103/ijpm.ijpm_33_22 -
Blood Mar 2017Controlled regulation of lineage decisions is imperative for hematopoiesis. Yet, the molecular mechanisms underlying hematopoietic lineage choices are poorly defined....
Controlled regulation of lineage decisions is imperative for hematopoiesis. Yet, the molecular mechanisms underlying hematopoietic lineage choices are poorly defined. Colony-stimulating factor 1 (CSF-1), the cytokine acting as the principal regulator of monocyte/macrophage (M) development, has been shown to be able to instruct the lineage choice of uncommitted granulocyte M (GM) progenitors toward an M fate. However, the intracellular signaling pathways involved are unknown. CSF-1 activates a multitude of signaling pathways resulting in a pleiotropic cellular response. The precise role of individual pathways within this complex and redundant signaling network is dependent on cellular context, and is not well understood. Here, we address which CSF-1-activated pathways are involved in transmitting the lineage-instructive signal in primary bone marrow-derived GM progenitors. Although its loss is compensated for by alternative signaling activation mechanisms, Src family kinase (SFK) signaling is sufficient to transmit the CSF-1 lineage instructive signal. Moreover, c-Src activity is sufficient to drive M fate, even in nonmyeloid cells.
Topics: Animals; Cell Lineage; Cells, Cultured; Granulocyte Precursor Cells; Hematopoiesis; Macrophage Colony-Stimulating Factor; Mice; Monocytes; Signal Transduction; src-Family Kinases
PubMed: 28159742
DOI: 10.1182/blood-2016-05-714329 -
Journal of Leukocyte Biology Feb 2004Alpha-defensins are antimicrobial peptides that contribute to innate-immune functions of neutrophils and intestinal Paneth cells. Transcription of alpha-defensin genes...
Alpha-defensins are antimicrobial peptides that contribute to innate-immune functions of neutrophils and intestinal Paneth cells. Transcription of alpha-defensin genes occurs early in neutrophilic myelopoeisis. To examine the mechanisms that regulate alpha-defensin gene expression, we analyzed transcription of rat neutrophil alpha-defensin NP-3 in D4 cells, a subclone of the promyelocytic cell line IPC-81. Northern blot analysis showed that D4 cells express fivefold higher levels of alpha-defensin mRNA than the parental cell line in a manner relatively independent of passage number. Increased levels of steady-state mRNA in D4 cells correlated with markedly elevated peptide levels detected by immunocytochemical staining. To identify the cis-acting DNA elements involved in tissue-specific expression, D4 cells were transfected with luciferase reporter constructs containing NP-3 gene 5'-flanking sequences. Analyses of transfected D4 cells demonstrated that the proximal 87 base pair (bp) sequence contained cis-acting DNA elements necessary for optimal promoter activity. Mutational analyses within the 87-bp region suggested the involvement of the CAAT box and a putative polyoma enhancer-binding protein 2/core-binding factor (PEBP2/CBF) site in defensin gene transcription. Transient transfection analyses using tandem repeats of oligonucleotides containing these sequences demonstrated that proximity of the CAAT box and PEBP2/CBF site was important for defensin promoter activity. Electrophoretic mobility shift assays indicated that PEBP2/CBF or a PEBP2/CBF-related protein was involved in a specific protein-DNA interaction occurring within a DNA fragment containing the CAAT and PEBP2/CBF sequences. These data identify functional trans- and cis-elements that regulate rat defensin gene expression in high defensin-expressing promyelocytic cells.
Topics: Animals; Cell Line; Clone Cells; Gene Expression Regulation; Genes, Regulator; Granulocyte Precursor Cells; Mutation; Myelopoiesis; Neutrophils; Promoter Regions, Genetic; Rats; Transfection; alpha-Defensins
PubMed: 14634060
DOI: 10.1189/jlb.0803384 -
Leukemia Feb 2023Mutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they...
Mutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. However, the role of ASXL1 in myeloid lineage maturation is incompletely described. To define the role of ASXL1 in myelopoiesis, we employed single cell RNA sequencing and a murine model of hematopoietic-specific Asxl1 deletion. In granulocyte progenitors, Asxl1 deletion leads to hyperactivation of MYC and a quantitative decrease in neutrophil production. This loss of granulocyte production was not accompanied by significant changes in the landscape of covalent histone modifications. However, Asxl1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator in myeloid development.
Topics: Animals; Humans; Mice; Granulocyte Precursor Cells; Mutation; Myelodysplastic Syndromes; Repressor Proteins; RNA Polymerase II; Transcription Factors
PubMed: 36526735
DOI: 10.1038/s41375-022-01792-x -
Development (Cambridge, England) Sep 2021Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling...
Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling neutrophil differentiation remains incompletely understood. GFI1 is associated with several myeloid disorders, but its role and the role of its co-regulators in granulopoiesis and pathogenesis are far from clear. Here, we demonstrate that zebrafish gfi1aa deficiency induces excessive neutrophil progenitor proliferation, accumulation of immature neutrophils from the embryonic stage, and some phenotypes similar to myelodysplasia syndrome in adulthood. Both genetic and epigenetic analyses demonstrate that immature neutrophil accumulation in gfi1aa-deficient mutants is due to upregulation of cebpa transcription. Increased transcription was associated with Lsd1-altered H3K4 methylation of the cebpa regulatory region. Taken together, our results demonstrate that Gfi1aa, Lsd1 and cebpa form a regulatory network that controls neutrophil development, providing a disease progression-traceable model for myelodysplasia syndrome. Use of this model could provide new insights into the molecular mechanisms underlying GFI1-related myeloid disorders as well as a means by which to develop targeted therapeutic approaches for treatment.
Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cell Proliferation; DNA-Binding Proteins; Embryo, Nonmammalian; Epigenesis, Genetic; Granulocyte Precursor Cells; Hematopoiesis; Histone Demethylases; Neutrophils; Zebrafish; Zebrafish Proteins
PubMed: 34373913
DOI: 10.1242/dev.199516 -
Blood Feb 2014CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of...
CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of secondary granule proteins, but it also regulates proliferation, cell cycle, and maturation during granulopoiesis. Cebpe(-/-) mice have incomplete granulocytic differentiation and increased sensitivity toward bacterial infections. The amount of C/EBP-ε messenger RNA (mRNA) increases with maturation from myeloblasts with peak level in myelocytes (MC)/metamyelocytes (MM), when the cells stop proliferating followed by a decline in more mature cells. In contrast, C/EBP-ε protein is virtually detectable only in the MC/MM population, indicating that expression in more immature cells could be inhibited by microRNAs (miRNAs). We found that miRNA-130a (miR-130a) regulates C/EBP-ε protein expression in both murine and human granulocytic precursors. Overexpression of miR-130a in a murine cell line downregulated C/EBP-ε protein and lactoferrin (Ltf), cathelicidin antimicrobial protein (Camp), and lipocalin-2 (Lcn2) mRNA expression giving rise to cells with a more immature phenotype, as seen in the Cebpe(-/-) mouse. Introduction of a C/EBP-ε mRNA without target site for miR-130a restored both C/EBP-ε production, expression of Camp and Lcn2, and resulted in the cells having a more mature phenotype. We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-ε during granulopoiesis.
Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cells, Cultured; Gene Expression Regulation; Granulocyte Precursor Cells; Granulocytes; HEK293 Cells; Humans; Leukopoiesis; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; NIH 3T3 Cells
PubMed: 24398327
DOI: 10.1182/blood-2013-08-523233 -
Clinical Advances in Hematology &... Jun 2007
Topics: Antineoplastic Agents; Erythropoietin; Female; Granulocyte Precursor Cells; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Male; Myelodysplastic Syndromes; Thalidomide
PubMed: 17679919
DOI: No ID Found -
Scientific Reports Apr 2021Extracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles...
Extracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. The dHL-60 cells are also easily loaded with various cargoes such as antibiotics (penicillin), anticancer drug (paclitaxel), chemoattractant (MCP-1), miRNA, and Cas9. The EVs derived from the dHL-60 cells showed efficient incorporation of these cargoes and significant effector functions, such as bactericidal activity, monocyte chemotaxis, and macrophage polarization. Our results suggest that neutrophils or neutrophil-like promyelocytic cells could be an attractive source for drug-delivery EVs.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Cell Communication; Cell Differentiation; Cells, Cultured; Chemokine CCL2; Drug Delivery Systems; Extracellular Vesicles; Granulocyte Precursor Cells; Humans; Neutrophils; Paclitaxel; Penicillins
PubMed: 33859336
DOI: 10.1038/s41598-021-87891-8