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International Journal of Hematology Dec 2015We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed... (Review)
Review
We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed with MS, as the tumor cells were positive for myeloperoxidase and CD68 but negative for CD163. After treatment with steroids and radiation, the size of the tumor was markedly reduced and peripheral blood count was normal. Bone marrow examination showed 89.2% consisted of unclassified promyelocytes characterized by round nuclei and abundant small azurophilic granules but no Auer rods. The results of chromosome analysis showed 46,XY,t(5;17)(q35;q12). Reverse-transcription polymerase chain reaction amplified the NPM1/RARA fusion transcripts derived from a combination of NPM1 exon 4 and RARA exon 5, or of NPM1 exon 1 and RARA exon 5; the latter of these has not been reported previously. Electron microscopic examination of the promyelocyte nuclei showed they were oval with mild nuclear chromatin condensation and small- to medium-sized nucleoli. Hematological and molecular complete remission was attained after induction therapy including all-trans retinoic acid. As MS was also diagnosed in two of the seven other reported cases of APL with NPM1/RARA, MS may occur more frequently in APL with NPM1/RARA than APL with PML/RARA.
Topics: Cell Nucleolus; Cell Nucleus; Chromatin; Exons; Gene Fusion; Granulocyte Precursor Cells; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Magnetic Resonance Imaging; Male; Microscopy, Electron; Middle Aged; Nuclear Proteins; Nucleophosmin; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Myeloid; Tretinoin
PubMed: 26342691
DOI: 10.1007/s12185-015-1857-2 -
British Journal of Haematology Jul 2021
Topics: Aged; Anemia, Sideroblastic; Bone Marrow; Erythroid Precursor Cells; Granulocyte Precursor Cells; Humans; Inflammation; Male; Mutation, Missense; Point Mutation; Sweet Syndrome; Syndrome; Ubiquitin-Activating Enzymes; Vacuoles
PubMed: 33651376
DOI: 10.1111/bjh.17381 -
Current Research in Translational... May 2021Promyelocytic sarcoma is an uncommon solid tumor made up of myeloblasts. It is characterized, like acute promyelocytic leukemia (APL), by a chromosomal translocation...
Promyelocytic sarcoma is an uncommon solid tumor made up of myeloblasts. It is characterized, like acute promyelocytic leukemia (APL), by a chromosomal translocation t(15;17) involving the retinoic acid receptor alpha (RARalpha) and the promyelocytic gene (PML). The diagnosis and monitoring of promyelocytic sarcoma is a challenge due to the rarity and severity of the disease. We describe a case with several initial sites and without APL. The patient was monitored with regular 18F-FDG PET/CT from diagnosis to complete response. The evolution of PET/CT imageries was compared to the quantification of PML-RARα fusion gene by RQ-PCR. In promyelocytic sarcoma medical care, 18F-FDG PET/CT appears to be an attractive tool for finding targets for biopsy, for the primary staging, for assessing therapeutic response and for detecting early relapse.
Topics: Fluorodeoxyglucose F18; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Positron Emission Tomography Computed Tomography; Sarcoma
PubMed: 33476934
DOI: 10.1016/j.retram.2020.103272 -
BMC Genomics Aug 2007Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where multipotent stem cells gradually limit their...
BACKGROUND
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where multipotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization.
RESULTS
Gene expression data from 24 experiments for 8 different cell types of the human myelopoietic lineage were used to generate an integrated myelopoiesis dataset of 9,425 genes, each reliably associated to a unique genomic position and chromosomal coordinate. Lists of genes constitutively expressed or silent during myelopoiesis and of genes differentially expressed in commitment phase of myelopoiesis were first identified using a classical data analysis procedure. Then, the genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. This approach allowed identifying specific chromosomal regions significantly highly or weakly expressed, and clusters of differentially expressed genes and of transcripts related to specific functional modules.
CONCLUSION
The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Topics: Antigens, CD34; Cell Differentiation; Cell Lineage; Chromosomes, Human; Cluster Analysis; Computational Biology; Eosinophils; Erythroblasts; Fetal Blood; Gene Expression; Gene Expression Profiling; Genome, Human; Genomics; Granulocyte Precursor Cells; Hematopoietic Stem Cells; Humans; Models, Biological; Monocytes; Myeloid Cells; Myelopoiesis; Neutrophils; Oligonucleotide Array Sequence Analysis; Software
PubMed: 17683550
DOI: 10.1186/1471-2164-8-264 -
Pathology Feb 2020
Topics: Bone Marrow; Granulocyte Precursor Cells; Humans; Immunophenotyping; Leukemia; Leukocyte Count
PubMed: 31883670
DOI: 10.1016/j.pathol.2019.09.021 -
Pathology Aug 2019Measurable residual disease (MRD) status of patients undergoing treatment for acute myeloid leukaemia (AML) is important for prognosis and guides treatment. Multicolour...
Measurable residual disease (MRD) status of patients undergoing treatment for acute myeloid leukaemia (AML) is important for prognosis and guides treatment. Multicolour flow cytometry (MCF) is a sensitive MRD method. The current approach relies on identification of blasts expressing leukaemia-associated immunophenotypes (LAIP) or by blasts expressing aberrant differentiation/maturation profiles compared to that seen in normal haematopoietic precursor cells at follow-up, i.e., different from normal (DFN). However, expression of LAIP on normal myeloblasts affects the specificity of the result, and the understanding of what is normal is important. Limited published data are currently available. We report findings from 14 normal adult bone marrows. MCF was performed on the residual normal marrow specimens from 14 adults. Expression of CD15, CD11b, CD7, CD4, and CD56 on CD34+ myeloblasts was assessed. Analysis of samples was performed using 4-colour flow cytometry which was the methodology used when this work was done, and is still being used in many clinical flow laboratories worldwide. LAIP is defined by lineage infidelity or asynchronous expression of differentiation markers. The cases of normal myeloblasts with LAIP involving the markers used and above the cut-off levels for MRD detection (0.01%) varies between 43% and 100%, limiting the specificity of the results for MRD. Even if the threshold is raised to 0.1%, there will still be false positive cases using aberrant CD15 or CD7. Our work provided useful information for AML MRD determination in our laboratory. A collaborative database of LAIP on normal myeloblasts using standardised analysis should be useful to determine the optimal diagnostic cut-off for AML MRD using LAIP.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Marrow; Female; Granulocyte Precursor Cells; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasm, Residual; Young Adult
PubMed: 31262563
DOI: 10.1016/j.pathol.2019.03.010 -
Journal of Hematology & Oncology May 2014MicroRNAs (miRNAs) are coordinators of cellular differentiation, including granulopoiesis. Although differential expression of many miRNAs is associated with the...
BACKGROUND
MicroRNAs (miRNAs) are coordinators of cellular differentiation, including granulopoiesis. Although differential expression of many miRNAs is associated with the maturation of granulocytes, analysis of differentially expressed miRNAs and their cellular localization across all stages of granulopoiesis, starting from hemopoietic stems cells, is not well characterized.
METHODS
We analyzed whole cell miRNA and mRNA expression during granulopoiesis using Taqman low-density and Affymetrix arrays respectively. We also performed nuclear and cytoplasmic fractionation followed by Taqman low-density array and/or quantitative PCR to identify nuclear-enriched miRNAs in hemopoietic stem/progenitor cells, promyelocytes, myelocytes, granulocytes and several hemopoietic cell lines. Anti-correlation between the expression of miRNA and target pairs was used to determine putative miRNA targets.
RESULTS
Analyses of our array data revealed distinct clusters of differentially expressed miRNAs that are specific to promyelocytes and granulocytes. While the roles of many of these miRNAs in granulopoiesis are not currently known, anti-correlation of the expression of miRNA/mRNA target pairs identified a suite of novel target genes. Clusters of miRNAs (including members of the let-7 and miR-17-92 families) are downregulated in hemopoietic stem/progenitor cells, potentially allowing the expression of target genes known to facilitate stem cell proliferation and homeostasis. Additionally, four miRNAs (miR-709, miR-706, miR-690 and miR-467a*) were found to be enriched in the nucleus of myeloid cells and multiple hemopoietic cell lines compared to other miRNAs, which are predominantly cytoplasmic-enriched. Both miR-709 and miR-706 are nuclear-enriched throughout granulopoiesis and have putative binding sites of extensive complementarity downstream of pri-miRNAs. Nuclear enrichment of miR-467a* is specific to hemopoietic stem/progenitors and promyelocytes. These miRNAs are also nuclear-enriched in other hemopoietic cell lines, where nuclear sequestering may fine-tune the expression of cytoplasmic mRNA targets.
CONCLUSIONS
Overall, we have demonstrated differentially expressed miRNAs that have not previously been associated with hemopoietic differentiation and provided further evidence of regulated nuclear-enrichment of miRNAs. Further studies into miRNA function in granulocyte development may shed light on fundamental aspects of regulatory RNA biology and the role of nuclear miRNAs.
Topics: Animals; Cell Line; Cell Nucleus; Cells, Cultured; Cytoplasm; Gene Expression Profiling; Gene Expression Regulation, Developmental; Granulocyte Precursor Cells; Granulocytes; Hematopoiesis; Hematopoietic Stem Cells; Humans; Mice; Mice, Inbred C57BL; MicroRNAs; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 24886830
DOI: 10.1186/1756-8722-7-42 -
Journal of Korean Medical Science Apr 2004The involvement of central nervous system is rare in acute promyelocytic leukemia (APL). We report a APL patient of a 41 yr-old Korean male who presented with fever and... (Review)
Review
The involvement of central nervous system is rare in acute promyelocytic leukemia (APL). We report a APL patient of a 41 yr-old Korean male who presented with fever and petechia. Complete molecular remission was achieved with all-trans retinoic acid (ATRA), idarubicin, and cytarabine. Ten months later, he complained of a mild headache. The results of the physical examination and the complete blood counts were normal. The examination of cerebrospinal fluid showed the presence of promyelocyte. Bone marrow studies showed cytogenetic remission but with molecular relapse. He was treated with intrathecal and systemic chemotherapy.
Topics: Adult; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Male; Meninges; Recurrence
PubMed: 15082912
DOI: 10.3346/jkms.2004.19.2.311 -
American Journal of Hematology Aug 2020
Topics: Anemia, Myelophthisic; Betacoronavirus; COVID-19; Coronavirus Infections; Erythroblasts; Female; Granulocyte Precursor Cells; Humans; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32212392
DOI: 10.1002/ajh.25793 -
Methods in Molecular Biology (Clifton,... 2021Salmonella enterica is a Gram-negative intracellular pathogen that causes a range of life-threatening diseases in humans and animals worldwide. In a systemic infection,...
Salmonella enterica is a Gram-negative intracellular pathogen that causes a range of life-threatening diseases in humans and animals worldwide. In a systemic infection, the ability of Salmonella to survive/replicate in macrophages, particularly in the liver and spleen, is crucial for virulence. Transformed macrophage cell lines and primary macrophages prepared from mouse bone marrow are commonly used models for the study of Salmonella infection. However, these models raise technical or ethical issues that highlight the need for alternative methods. This chapter describes a technique for immortalizing early hematopoietic progenitor cells derived from wild-type or transgenic mice and using them to produce macrophages. It validates, through a specific example, the interest of this cellular approach for the study of Salmonella infection.
Topics: Animals; Cell Line, Transformed; Cell Line, Tumor; Granulocyte Precursor Cells; Homeodomain Proteins; Liver; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Salmonella Infections; Salmonella enterica; Spleen; Virulence
PubMed: 32894491
DOI: 10.1007/978-1-0716-0791-6_11