DOCSLIB.ORG

Expression of Cytokine Genes, Cytokine Receptor Genes, and Transcription Factors in Cultured Hodgkin and Reed-Sternberg Cells1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Expression of Cytokine Genes, Cytokine Receptor Genes, and Transcription Factors in Cultured Hodgkin and Reed-Sternberg Cells1 [CANCER RESEARCH 52, 3353-3360, June 15, 1992] Expression of Cytokine Genes, Cytokine Receptor Genes, and Transcription Factors in Cultured Hodgkin and Reed-Sternberg Cells1 Hans-JürgenGruss, Marion A. Brach, Hans-GünterDrexler, Renate Bonifer, Roland H. Mertelsmann, and Friedhelm Herrmann2 Department of Internal Medicine I, University of Freiburg Medical Center, Freiburg [H-J. G.,M.A. B., R. B., R. H. M.,F. H.], and German Collection of Microorganisms and Cell Cultures [H-G. D.J, Braunschweig, Germany ABSTRACT 2 for review). Various cell types have been proposed as the originators of HD including lymphoid cells (3-6), mononuclear In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived phagocytes (7-11 ), interdigitating reticulum cells (12), follicular cell lines HDLM-2 and KM-H2 express a variety of cytokine genes dentritic cells (13, 14), and granulopoietic cells (15). Unfortu either constitutively or upon induction with phorbol ester 12-O-tetrade- nately, the analysis of RS-H cells is hampered by the scarcity canoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines of this neoplastic component and contamination with bystander include granulocyte-macrophage colony-stimulating factor (( 'SI1'),mac- cells in HD-involved tissues. The advent of improved tissue rophage-CSF, interleukin (II,)-!-,». II -X IL-5, II -6, IL-8, leukemia culture methodology for the establishment of immortalized cell inhibitory factor, tumor necrosis factor-«,tumor necrosis factor-/?, and lines has enhanced the possibilities of studying neoplastic cells. transforming growth factor-/?, while transcripts and the corresponding Recently, a number of cell lines have been established from proteins for granulocyte-CSF, IL-1-/3, IL-2, IL-4, IL-7, IL-10, and the tissues or pleural effusions of patients with HD (16-21), mostly JE/macrophage chemoattractant and activating factor gene were not with the nodular sclerosis variant. These in vitro cultured cells detectable in cytoplasmic RNA and culture supernatants obtained from may represent the in vivo RS-H cells having identical or very both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c- fmx) genes were expressed by both lines. HDLM-2, but not KM-H2 similar characteristic features. Therefore, they might be opera cells, exhibited the II -6 R p80 and the IL-2 R p75 chain. Analysis of tionally regarded as in vitro representatives of RS-H cells, nuclear proteins that bind to oligonucleotides containing the consensus although it has to be considered that cell lines cannot be derived sequences of the transcription factors activation protein 1, nuclear factor from the vast majority of cases of HD, and therefore, HD (NF) <cB,and NFAT 1 revealed a pattern for HD lines resembling that tumors that allow establishment of cell lines may somehow •¿ofactivatedT-cells: HDLM-2 and KM-H2 cells constitutively expressed bear atypical features. NF binding to the NF of activated T-cells (type 1), previously described Recent studies aimed at determining the precursor identity to be T-cell specific. In addition, NF «B-bindingproteins obtained from of RS-H cells and the pathogenesis of HD have focused on both lines showed, in electrophoretic mobility shift assays, the same phenotypic studies (see Ref. 22 for review) and molecular migration pattern as T-cell-derived proteins but differed from monocyte- genetic studies of rearrangements of the T-cell receptor and and B-cell-derived proteins. IV cross-linking experiments confirmed that immunoglobulin genes (23-26), have analyzed possible altera NF xB-binding proteins of M, 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, tions of the genomic structure and expression levels of certain while monocytes and B-cells displayed the M, 50,000/55,000 and 75,000 protooncogenes including those of the ras gene family (27, 28), NF *H complex only. Both HD lines also constitutively expressed tran of the c-myc gene (16, 29) and the c-fms gene (30, 31), and have scripts for i--fiisand c-jun, which are involved in heterodimeric formation also explored the presence of Ebstein-Barr virus DNA in RS- of the transcription factor activation protein 1, as well as for the NF «B/ H cells. In most of these studies, HD-derived cell lines were KBF1 gene. used. Despite these extensive efforts, there is still no consensus concerning either the etiology of HD or the identity of RS-H INTRODUCTION cells. Characterization of further features of HD-derived cell lines would thus be important in increasing our understanding HD3 is a malignant disorder morphologically characterized of HD. by the presence of multinucleated RS and the mononuclear H A number of features of HD are consistent with characteris cells in a stremai background consisting of lymphocytes, plasma tics of a tumor of cytokine-producing cells, including occurrence of "B" symptoms, of sclerosis, eosinophilia, and polycarion cells, histiocytic cells, and eosinophils (1). Both the etiology of HD and the precursor identity of its presumed malignant com formation. Several investigators have assessed the capacity of ponent, the RS and H cells, have remained uncertain (see Ref. RS-H cells to express cytokine genes. For instance, Paietta et al. (31) have shown that the L428 cell line, obtained from a Received 12/10/91; accepted 4/6/92. nodular sclerosis HD patient, disclosed transcripts for the M- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in CSF and its receptor, encoded by the c-fms protooncogene (32). accordance with 18 U.S.C. Section 1734 solely to indicate this fact. CSF secretion by cultured H-RS cells has also been shown by 1Supported by the Deutsche Krebshilfe. 2To whom requests for reprints should be addressed, at Department of Internal Burrichter et al. (33) and Byrne et al. (34). Naumovski et al. Medicine I. University of Freiburg Medical Center, Hugstetter Str. 55, D-7800 (35) have described secretion of IFN--y by the SUP-HD1 cell Freiburg i.Br., Germany. line. By means oíinsitu hybridization, transcripts for IL-5 were 3The abbreviations used are: HD, Hodgkin's disease; RS, Reed-Sternberg; H, Hodgkin; CSF, colony-stimulating factor; M-CSF, macrophage CSF; IFN. inter- detected in RS cells of primary HD tissues by Samoszuk and feron; TNF, tumor necrosis factor; GM-CSF, granulocyte-macrophage CSF; G- Nansen (36). Hsu et al. (37-39) have analyzed expression of CSF, granulocyte CSF; IL, interleukin; LIF, leukemia inhibitory factor; TGF, IL-1, TNF-a, and TNF-0 in the HDLM-1 and HDLM-ld transforming growth factor; JE/MCAF, JE/macrophage chemoattractant and Hodgkin lines (37-39). Similarly, Kretschmer et al. (40) have activating factor; cDNA complementary DNA; AP, activation protein; NF, nu clear factor; NFAT 1, nuclear factor of activated T-cells; EMSA, electrophoretic shown the ability of L428 and L540 Hodgkin cells to produce mobility shift assay; TPA, l2-O-tetradecanoylphorbol-13-acetate; moAb, mono TNF. TGF-/3 and IL-6 secretion by RS-H cells has also been clonal antibody; TCR, T-cell receptor; ATCC, American Type Culture Collection; SDS, sodium dodecyl sulfate; SSC, standard sodium citrate; IL-2R (IL-6R), IL- demonstrated in both cultured and primary Hodgkin tissues 2 (IL-6) receptor. (41-43). Also, expression of IL-9 by cultured and primary RS- 3353 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1992 American Association for Cancer Research. CYTOKINES IN HODGKIN'S DISEASE H cells has been shown (44, 45). kilobase Taql/BanU fragment of pGEM4-hIL-6 (kindly provided by T. Given these first observations, the aim of the present study Hirano, University of Osaka, Osaka, Japan); IL-7, the 0.51-kilobase was to examine the spectrum of cytokines released by the two Pvull fragment of pGembl-hIL-7 (S. Gillis); IL-8, the 0,4-kilobase well-defined HD-derived permanent cell lines HDLM-2 (46) Bglll/EcoRl fragment of pBBG44 (British Bio-Technology, Oxford, and KM-H2 (47) in more detail. To this end, an extensive panel United Kingdom); IL-10, the 0.76-kilobase Bgm/Hindlll fragment of pcDSRa (kindly provided by P. Vieira, DNAX Research Institute of of cytokines was analyzed at the mRNA and protein levels, Molecular and Cellular Biology, Palo Alto, CA); JE/MCAF, the 0.74- including GM-CSF, G-CSF, M-CSF, IL-1-«and IL-1-/3, IL-2, kilobase Kpnl fragment of pGEM-hJE34 (kindly provided by B. Rollins, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, LIF, TNF-a, TNF-0, Dana-Farber Cancer Institute, Boston, MA); LIF, the 0.6-kilobase TGF-/3, IFN-7, the gene coding for the JE/MCAF protein, and ///nrfIII/£coRI fragment of pBBG 46 (British Bio-Technology); TNF- the early response genes c-jun and c-fos, known to be involved a, the 1.0-kilobase Psll fragment of pSP64-hTNF-a (kindly provided in cytokine signaling (48, 49). In addition, expression of the by G. Adolph, Boehringer International, Vienna, Austria); TNF-/3, the p55 IL-2R a and p75 ßchain,of the p80 IL-6R, and of the M- 0.6-kilobase Ndel/BgllI fragment of pBBGS (British Bio-Technology); CSF receptor (c-fms) was assessed by Northern blotting using IFN-7, the 0.7-kilobase AamHI fragment of pBR322-hIFN-7 (Genen- tech, San Francisco, CA); TGF-/J, the 1.04-kilobase £coRIfragment of specific cDNA probes. The presence of transcription factors known to bind to consensus sequences in regulatory 5'-flanking pSP 64 (Genentech); c-fms, the 1.23-kilobase £coRIfragment of pcfms 104 (ATCC); NF «B/KBF1,the 3.9-kilobase Noti insert of pBKS-«BFl regions of many cytokine genes (50), such as the AP 1, the NF (kindly provided by S.
Load more

Recommended publications
  • A Comparative Study of Murine Mast Cell Progenitors
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2001 A Comparative Study of Murine Mast Cell Progenitors Shirley K. DeSimone Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Other Medicine and Health Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/4529 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Virginia Commonwealth University School of Medicine This is to certifythat the dissertation prepared by Shirley K. DeSimone entitled "A Comparative Study of Murine Mast Cell Progenitors" has been approved by her committee as satisfactory completion of the disse1tation requirement for the degree of Doctor of Philosophy. Francine M. Marciano-Cabral, Ph.D., School of Medicine Jack L. Haar, Ph.D., Dean, School of Graduate Studies A Comparative Study of Murine Mast Cell Progenitors A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University By Shirley K. DeSimone Director: Thomas F. Huff, Ph.D. Professor, Microbiology and Immunology Virginia Commonwealth University Richmond, Virginia May, 2001 11 Acknowledgments I wish to thank my advisor, Dr. Thomas F. Hufffor his insight, guidance, and patience. also which to acknowledge the invaluable, unwavering, and loving support of my husband, friend and companion, Dr. John A. DeSimone. Thanks are also due to the consistently helpful graduate students of Dr.
    [Show full text]
  • Effects of Heterologous Antineutrophil Serum in Guinea Pigs Hematologic and Ultrastructural Observations
    Effects of Heterologous Antineutrophil Serum in Guinea Pigs Hematologic and Ultrastructural Observations David M. Simpson and Russell Ross Two pools of rabbit anti-guinea pig neutrophil serum (ANS) were prepared using an intravenous (ANS I) or subcutaneous (ANS II) route of immunization with proteose peptone-stimulated peritoneal exudate neutrophils (PMNs) from albino guinea pigs. In vitro, both pools of ANS contained high titers of agglutinating antibodies to neutrophils and lower titers against lymphocytes and red cells. Ag- glutinins against all three cell types could be selectively removed by absorption. The in vivo hematologic effects of both the absorbed and unabsorbed antisera were examined after intraperitoneal administration, and the effects of ANS on neu- trophils in blood, bone marrow, and peritoneal cavity were examined by light and electr microscopy of spleen, liver, lung, lymph node, buffy coat, bone mar- row and pellets of peritoneal cells removed at various time intervals within 24 hours. Injection of either antisera caused a rapid decrase in circulating neu- trophils and lymphocytes, whi reached thefr lowest levels within 12 hours. Neutrophils that disappeared from the circulation were sequestered primarily in liver and spleen where they were phagocytized, as morphologically intact cells, by macrophages and then rapidly digested. Immature bone marow neutrophils as young as early myelocytes were ingested by macrophages in the marrow at 6 hours or later after ANS. Neutrophils that were phagocytized were apparently opsonized by ANS since there was no ultrastructurl evidence of neutrophil lysis in blood or bone manrow after ANS treatment. However, both lysed and ingested neubrophils were observed in the peritoneal cavity.
    [Show full text]
  • 10 Maturation and Development of Leucocytes
    MODULE Maturation and Development of Leucocytes Hematology and Blood Bank Technique 10 Notes MATURATION AND DEVELOPMENT OF LEUCOCYTES 10.1 INTRODUCTION The leucocytes develop from the multipotent hematopoietic stem cell which then gives rise to a stem cell committed to formation of leucocytes. Both these cells cannot be identified morphologically by routine methods. The various types of leucocytes are granulocytes (neutrophils, eosinophils and basophils), monocytes and lymphocytes. The three cell types develop separately and accordingly these processes will be discussed separately. OBJECTIVES After reading this lesson, you will be able to: z explain the various stages in the development of leucocytes. z describe the different types of leucocytes seen normally in PBF. 10.2 MYELOPOIESIS This is the process of formation of myeloid cells. It is restricted to the bone marrow after birth. The committed progenitor cell for granulocytes and monocytes is the GM-CFU which proliferates and differentiates to form myeloblast and monoblast. The myeloblast is the earliest morphologically identifiable cell. It is 10-18µm in size. The cytoplasm is scant and basophilic, usually agranular and may contain a few azurophilic cytoplasmic granules in the blast transiting to the next stage 80 HEMATOLOGY AND BLOOD BANK TECHNIQUE Maturation and Development of Leucocytes MODULE of promyelocyte. It has a large round to oval nucleus with a smooth nuclear Hematology and Blood membrane. The chromatin is fine, lacy and is evenly distributed throughout the Bank Technique nucleus. Two-five nucleoli can be identified in the nucleus. The next stage of maturation is the Promyelocyte. It is larger than a myeloblast, 12-20 µm with more abundant cytoplasm which has abundant primary azurophilic granules .
    [Show full text]
  • Bleeding Fevers! Thrombocytopenia and Neutropenia
    Bleeding fevers! Thrombocytopenia and neutropenia Faculty of Physician Associates 4th National CPD Conference Monday 21st October 2019, Royal College of Physicians, London @jasaunders90 | #FPAConf19 Jamie Saunders MSc PA-R Physician Associate in Haematology, Guy’s and St Thomas’ NHS Foundation Trust Board Member, Faculty of Physician Associates Bleeding fevers; Thrombocytopenia and neutropenia Disclosures / Conflicts of interest Nothing to declare Professional Affiliations Board Member, Faculty of Physician Associates Communication Committee, British Society for Haematology Education Committee, British Society for Haematology Bleeding fevers; Thrombocytopenia and neutropenia What’s going to be covered? - Thrombocytopenia (low platelets) - Neutropenia (low neutrophils) Bleeding fevers; Thrombocytopenia and neutropenia Thrombocytopenia Bleeding fevers; Thrombocytopenia (low platelets) Pluripotent Haematopoietic Stem Cell Myeloid Stem Cell Lymphoid Stem Cell A load of random cells Lymphoblast B-Cell Progenitor Natural Killer (NK) Precursor Megakaryoblast Proerythroblast Myeloblast T-Cell Progenitor Reticulocyte Megakaryocyte Promyelocyte Mature B-Cell Myelocyte NK-Cell Platelets Red blood cells T-Cell Metamyelocyte IgM Antibody Plasma Cell Secreting B-Cell Basophil Neutrophil Eosinophil IgE, IgG, IgA IgM antibodies antibodies Bleeding fevers; Thrombocytopenia (low platelets) Platelet physiology Mega Liver TPO (Thrombopoietin) TPO-receptor No negative feedback to liver Plt Bleeding fevers; Thrombocytopenia (low platelets) Platelet physiology
    [Show full text]
  • Acute Monoblastic Leukemia with T(10;11)(P12;Q23) Presenting with Pulmonary Involvement: a Case Report and Literature Review
    Case Report Acute Monoblastic Leukemia with t(10;11)(p12;q23) Presenting with Pulmonary Involvement: A Case Report and Literature Review Kannadit Prayongratana MD*, Manaphol Kulpraneet MD*, Prapaporn Panichchob BSc**, Woraphot Tantisiriwat MD*** * Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Nakhon-nayok ** Department of Pathology, Faculty of Medicine, Srinakharinwirot University, Nakhon-nayok *** Department of Preventive and Social Medicine. Faculty of Medicine, Srinakharinwirot University, Nakhon-nayok A forty-three-year-old Thai man presented with acute fever and dyspnea for one week with bilateral patchy infiltration, pancytopenia with monoblast. Bone marrow study was consistent with acute monoblastic leukemia. Lung lesions rapidly progressed to acute respiratory failure, which required intubation. Broncho- scopy with bronchoalveolar lavage revealed monotonous monoblast infiltration. Induction chemotherapy with 7 + 3 regimen was administered to halt the progression of leukemic pulmonary infiltration. Although there was clinical improvement, the chest radiograph developed crescent formation in the right upper lung field. Invasive pulmonary aspergillosis was suspected and successfully treated with antifungal agent. After peripheral blood recovery, bone marrow evaluation was performed and complete remission was established. HLA matching was sent to prepare for hematopoietic stem cell transplantation (HSCT). The literature review showed that the appropriate treatment for the patients with t(10;11)(p12;q23) was HSCT, but there was no data concerning correlation of t(10;11)(p12;q23) and pulmonary infiltration. This may be due to the low incidence of leukemic infiltration of acute leukemia patients, which is 0.48% and 3.06% in acute myeloid leukemia and acute monoblastic leukemia, respectively. Keywords: Acute monoblastic leukemia, Leukemic pulmonary infiltration, t(10;11)(p12;q23) J Med Assoc Thai 2008; 91 (4): 559-63 Full text.
    [Show full text]
  • Blood Lab First Week
    Blood Lab First Week This is a self propelled powerpoint study atlas of blood cells encountered in examination of the peripheral blood smear. It is a requirement of this course that you begin review of these slides with the first day of class in order to familiarize yourself with terms used in describing peripheral blood morphology. Laboratory final exam questions are derived directly from these slides. The content of these slides may duplicate slides (1-37) listed on the Hematopathology Website. You must familiarize yourself with both sets of slides in order to have the best learning opportunity. Before Beginning This Slide Review • Please read the Laboratory information PDF under Laboratory Resources file to learn about – Preparation of a blood smear – How to select an area of the blood smear for review of morphology and how to perform a white blood cell differential – Platelet estimation – RBC morphology descriptors • Anisocytosis • Poikilocytosis • Hypochromia • Polychromatophilia Normal blood smear. Red blood cells display normal orange pink cytoplasm with central pallor 1/3-1/2 the diameter of the red cell. There is mild variation in size (anisocytosis) but no real variation in shape (poikilocytosis). To the left is a lymphocyte. To the right is a typical neutrophil with the usual 3 segmentations of the nucleus. Med. Utah pathology Normal blood: thin area Ref 2 Normal peripheral blood smear. This field is good for exam of cell morphology, although there are a few minor areas of overlap of red cells. Note that most cells are well dispersed and the normal red blood cell central pallor is noted throughout the smear.
    [Show full text]
  • *Fundad4o Gon(Alo M.1Oniz, Sal(Ador, Bahia, Brazil
    Br. J. exp. Path. (1981) 62, 480 HEPATIC EOSINOPHIL GRANULOCYTOPOIESIS IN MURINE EXPERIMENTAL SCHISTOSOMIASIS MANSONI R. BOROJEVIC*t, S. STOCKERt AND J. A. GRIMAUDt Fro0m the tinstitot Pasteur de Lyon, ERA 819, 77 Rue Pasteur, 69007 Lyon, France, and *Fundad4o Gon(alo M.1oniz, Sal(ador, Bahia, Brazil Received fo)p)ublicationlMay 27, 1981 Summary.-In livers of mice with acute schistosomiasis eosinophil granulocyto- poietic folliculi are described. Exogen stem cells were observed in hepatic sinusoids. Their proliferation and progressive maturation are described. Specific reactions to the presence of worms and their eggs, and Kupffer-cell stimulation and hyperplasia are considered to be responsible for this extramedullary granulocytopoiesis. AN INCREASE in the level of eosinophil Warren and Johnson (1967) and by granulocytes in blood, bone marrow and Bogitsh (1971), but the question of their involved tissues is characteristic of many origin was not solved. parasitic infections. It is particularly 3. In the hepatic parenchyma, inde- prominent in those in which parasites pendent of portal spaces and of periovular inhabit the circulatory system, or in which granulomas, folliculi can be observed, their life cycles include the passage of composed of mature eosinophils, together larvae through the host tissues (Basten, with immature forms and blastic cells. In Boyer and Beeson, 1970; Colley, 1972). earlier works, Goennert (1955), Grimaud Related to the presence and quantity of and Borojevic (1972) and Byram et al. parasite antigens in situ, eosinophilia is (1978) have interpreted these hepatic particularly high in the acute phase of folliculi in murine schistosomiasis as sites human (Diaz-Rivera et al., 1956) and in of local granulocytopoiesis.
    [Show full text]
  • 0Bb5e42028013d014ca1ac814e
    STUDIES ON THE MATURATION OF MYELOBLASTS INTO MYELOCYTES AND ON AMITOTIC CELL DIVISION IN THE PERIPHERAL BLOOD IN SUBACUTE MYELO- BLASTIC LEUCEMIA. By F. R. SABIN, M.D., C. R. AUSTRIAN, M.D., R. S. CUNNINGHAM, M.D., AND C. A. DOAN, M.D. (From the Department of Anatomy of the Johns Hopkins University, Baltimore.) PrAr~,s 39 AI~D40. (Received for publication, June 30, 1924.) INTRODUCTION. Through the courtesy of the Medical Department of the Johns Hopkins Medical School and of the Hebrew Hospital and Asylum of Baltimore, we have had the privilege of studying the blood in several cases of leucemia during the past 2 years. The case which forms the basis of this report was from the Hebrew Hospital, and the clinical history has been contributed to this article by its medical director, Dr. Charles R. Austrian. With the introduction of a new technique, by which differential studies of living blood cells can be made, it is of the utmost value to study the blood of leucemic patients from the standpoint of estab- lishing the morphology of the blood-forming organs on such a basis as to open up an experimental attack on the mechanism, first, of the regu- lation, of the normal proportion of different types of cells in the circu- lating blood and, second, of the alteration in disease of the proportion and indeed of the types of cells appearing in the blood. In the case reported here, we think that we were able to identify myeloblasts with the supravital technique, to demonstrate that the maturation of myeloblasts into myelocytes followed the transfusion of whole blood, and to identify the stages through which myeloblasts develop into myelocytes and finally into leucocytes.
    [Show full text]
  • Difference Between Promyelocyte and Myelocyte Key Difference
    Difference Between Promyelocyte and Myelocyte www.differencebetween.com Key Difference - Promyelocyte vs Myelocyte Granulated blood cells include eosinophils, basophils, and neutrophils which participate in a variety of functions in the body. The precursor stem cells of these cells which arise from the hematopoietic stem cells are of the myeloid lineage. Myeloblasts are the precursor cells of granulated blood cells. Myeloblasts then mature into promyelocytes, myelocytes, metamyelocytes, bands, and segments to finally give rise to granulocytes in the peripheral blood tissue. The development process is known as Granulopoiesis. Promyelocyte is the second stage of Myeloblast development. Myelocyte is the third stage of Myeloblast development. The key difference between the promyelocyte and the myelocyte is the level of differentiation it exhibits. Promyelocytes do not show differentiation while myelocytes show differentiation. What is a Promyelocyte? Promyelocyte is the second stage of the Myeloblast development process. The promyelocyte is larger than the myeloblast. It has a diameter of 12-25µm and is the largest cell type in the myeloid series. It has a prominent nucleus, and the nucleus is placed slightly intended in the cytoplasm. Chromatin and nucleoli are prominent in this. Final structures of chromatin can be identified through microscopic observations. Towards the complete maturation of the promyelocyte, the chromatins appear as well-condensed structures. The condensed chromatin is placed along the nuclear membrane. The cytoplasm of the promyelocyte is granulated, and these granules are termed as the primary azurophilic granules. Since the promyelocyte is not differentiated, it is formed of a basophilic cytoplasm. The cell organelle organization is prominent in the promyelocyte stage of the blood cells.
    [Show full text]
  • Bone Marrow Aspirate A Bone Marrow Film Should First Be Examined Macroscopically to Make Sure That Particles Or Fragments Are Present
    Aspiration of the BM Satisfactory samples can usually be aspirated from the Sternum Anterior or posterior iliac spines Aspiration from only one site can give rise to misleading information; this is particularly true in aplastic anaemia as the marrow may be affected partially. There is little advantage in aspirating more than 0.3 ml of marrow fluid from a single site for morphological examination as this increases peripheral blood dilution. Bone marrow aspirate A bone marrow film should first be examined macroscopically to make sure that particles or fragments are present. Bone marrow aspirates which lack particles may be diluted with peripheral blood and may therefore be unrepresentative. An ideal bone marrow film with particles is shown. Even films without fragments are worth examining as useful information may be gained. However, assessment of cellularity and megakaryocyte numbers is unreliable and dilution with peripheral blood may lead to lymphocytes and neutrophils being over- represented in the differential count. Erythroid series Myeloid series Megakaryocytic series *Proerythroblast **Early erythroblast ***Intermediate erythroblast ****Late erythroblast Erythroid precursors Normal red cells are produced in the bone marrow from erythroid precursors or erythroblasts. The earliest morphologically recognisable red cell precursor is derived from an erythroid progenitor cell which in turn is derived from a multipotent haemopoietic progenitor cell. proerythroblast Normal proerythroblast [dark red arrow] in the bone marrow. This is a large cell with a round nucleus and a finely stippled chromatin pattern. Nucleoli are sometimes apparent. The cytoplasm is moderately to strongly basophilic. There may be a paler staining area of cytoplasm surrounding the nucleus. Normal erythroblasts in the BM .
    [Show full text]
  • Myeloproliferative Neoplasms Myelofibrosis, Polycythemia Vera and Essential Thrombocythemia
    Myeloproliferative Neoplasms Myelofibrosis, Polycythemia Vera and Essential Thrombocythemia Ron, myelofibrosis Support for this publication provided by Revised 2017 A Message from Louis J. DeGennaro, PhD President and CEO of The Leukemia & Lymphoma Society The Leukemia & Lymphoma Society (LLS) is the world’s largest voluntary health organization dedicated to finding cures for blood cancer patients. Our research grants have funded many of today’s most promising advances; we are the leading source of free blood cancer information, education and support; and we advocate for blood cancer patients and their families, helping to ensure they have access to quality, affordable and coordinated care. Since 1954, we have been a driving force behind almost every treatment breakthrough for blood cancer patients. We have invested more than $1 billion in research to advance therapies and save lives. Thanks to research and access to better treatments, survival rates for many blood cancer patients have doubled, tripled and even quadrupled. Yet we are far from done. Until there is a cure for cancer, we will continue to work hard—to fund new research, to create new patient programs and services, and to share information and resources about blood cancers. This booklet has information that can help you understand myeloproliferative neoplasms, prepare your questions, find answers and resources, and communicate better with members of your healthcare team. Our vision is that, one day, all people with myeloproliferative neoplasms will either be cured or will be able to manage their disease so that they can experience a great quality of life. Today, we hope our expertise, knowledge and resources will make a difference in your journey.
    [Show full text]
  • Interpreting an Abnormal CBC
    Interpreting an Abnormal CBC Nicholas A. Forward MD, MSc, FRCPC Assistant Professor Division of Hematology Dalhousie University [email protected] Interpreting an Abnormal CBC – April 11, 2018 1 Disclosures • No conflicts of interest particularly relevant to this talk • Advisory Boards • Celgene • Co-/sub-investigator on a number therapeutic trials for various hematologic malignancies including leukemia, lymphoma, myeloma • Not discussing “off-label” medication use Interpreting an Abnormal CBC – April 11, 2018 2 Lecture Objectives • 1. Understand normal blood cell production at a very broad level • 2. Develop an initial approach to working up CBC abnormalities • Cytopenias • “-Cytosis” • 3. Recognize concerning complete blood count abnormalities • Recognize hematologic emergencies/red flags • When to refer and our local triage criteria Interpreting an Abnormal CBC – April 11, 2018 3 Refresher- Normal Hematopoiesis Bone marrow Normal bone marrow Interpreting an Abnormal CBC – April 11, 2018 4 Refresher- Normal Hematopoiesis Courtesy of Dr. Clinton Campbell, Hematopathology Interpreting an Abnormal CBC – April 11, 2018 5 Refresher- Normal Hematopoiesis Courtesy of Dr. Clinton Campbell, Hematopathology Interpreting an Abnormal CBC – April 11, 2018 6 Refresher- The Peripheral Blood Smear Courtesy of Dr. Clinton Campbell, Hematopathology Interpreting an Abnormal CBC – April 11, 2018 7 Refresher – The bone marrow Normal bone marrow Interpreting an Abnormal CBC – April 11, 2018 8 Refresher- CBC Parameters Parameter Normal Range* Units WBC
    [Show full text]