Bone Marrow Stroma in Myelodysplastic Syndromes
|
|
- Dylan Stone
- 6 years ago
- Views:
Transcription
1 Bone Marrow Stroma in Myelodysplastic Syndromes Universidad de Salamanca Prof Mª M Consuelo del Cañizo Hematology Dept. University Hospital, Salamanca SPAIN
2 Bone marrow stroma in MDS Introduction Mesenchymal stem cells Mesenchymal stem cells in MDS: Morphological and functional data Genomic features
3 MDS Characteristics -- Hipercellular bone marrow -- Perypheral cytopenias -- Morphological dyshemopoiesis -- Genetic instability -- Transformation to saml Impaired Hematopoiesis
4 HPC Stromal cells In hematopoiesis both, HPC as well as stromal BM cells are involved
5 In MDS pathophysyology various mechanisms are involved Growth factors Epigenetic and genetic mechanisms Apoptosis Monocyte Macrophage HSC: clonal expansion Autocrine mechanism TNF-, TGF- IFN-, IL1-b T Lymphocytes: Immunological disregulation MSC Paracrine mechanism Microenvironment Fibronectine Vessels The role of microenvironment is getting a great deal of interest.
6 Mesenchymal stem cells They constitute % 0.01% of the BM cells. They are the BM stromal progenitors They can be easily isolated and expanded They are key cells for hematopoietic maintenance.
7 BM microenvironment in MDS 1.Capacity to support hematopoiesis: Discordant results 2.Abnormal secretion of chemo- and cytokine : TNFa; IL6; VEGF IFNg IL32 32, SCF; LIF 3.Abnormal cell balance. Increased microvasculature Increased EPC Increased number of osteoblasts Alvi et al Leuk Res 2001 Tauro et al, Leukemia 2002 Campioni et al. Leuk Res 2004 Borojevic et al. Leuk Res 2004 Marcondes et al. PNAS 2008 Working Hypothesis 1. Hematopoiesis is impaired in MDS at both levels, HPC and BM microenvironment 2. Mesenchymal stem cells are the BM stromal progenitors 3. Could MSCs be functionally and/or genomically abnormal?
8 Patients and controls Patients. N- 76 M/F: 41 / 35 Age: median 72 (34-92) Controls 36 healthy volunteers M/F: 20 / 16 Age : median 60 (37-88) Cytogenetics N Normal 29 Abnormal 47 5q-: 30 +8: 14
9 MSCs from MDS: In vitro growth Cell growth: 6/32 non confluent cultures Longer time to reach confluence: Controls 15 d.. (11( 11-30) MDS 23,5 d.. (12( 12-90) 32 80,00 p<0.05 MDS Days DiasPase until passage 60,00 40, ,00 Contol 1,00 2,00 SanoSMD MDS Control
10 Are these features produced by reduced proliferation or increased apoptosis? G0/G1:97.42 % Channels (FL2-A-FL2-Area ) Número S: 0.6% G2/M: 1.98% A tendency to higher Cell cycle was similar in both groups A tendency to higher apoptosis was shown by MDS MSCs 7AAD 24% FL3-Height -> AnexinaV
11 CD 105 Phenotypical data Normal expression for: CD90 90, 73, 166, 106, 54, 56 49a, 49b, 34, 45, 19,14.117, 133, HLA-DR Lower expression of CD105 (endoglin) y CD104 (beta integrin). (p<0.05( 0.05) MDS Control Cell purity >98% CD 104 MDS Control 25,00 1,60 20,00 p<0.05 1,40 1,20 p<0.05 cd105fl1 15,00 10,00 4 fl2 0 1,00 1 d c 0,80 5,00 0,60 0,00 0,40 Control donante diagnostico MDS SMD MDS Control donante Control diagnostico MDS SMD MDS MSCs from MDS patients show an abnormal growth capacity as well as an abnormal expression of some surface molecules
12 MSCs shows genomic changes?: Analysis using CGH-arrays Expanded MSCs (N=13): 100% showed genomic abnormalities 19p % 11q % 20q % 1q % 3q % 4q % Genomic gains were more frequent 7p22 23% 7q % 17q % 19p % 19q % 21q % Genomic losses 7q % BAC RPCI G2: 1q Genomic changes are not polymorphisms FISH analysis using the same BAC Expanded MSCs show genomic changes CGH Arrays also performed: T- lymphocytes: they are not constitutional changes. HPC: they are not present in HPC
13 MSC-MDS CGH arrays: Unsupervised analysis Cluster I N WHO 1 RAEB-2 1 RCMD-RS 1 umds Cytogenetics +8 Normal Normal N 5 1 WHO MDS 5q- RA Cluster II Cytogenetics 5q- 4% 5q- 2 RAEB-e Normal 1 1 RARS RAEB q- Marrow morphological features compatible with 5q- syndrome MSCS from 5q- syndrome are different from those from other MDS
14 MSC-MDS enrichment by cell sorting Fresh bone marrow samples + Fraction BM Lysis CD45/CD73/ CD34/CD271 Sorter - Fraction Cell purity >99% CD73 CD45 45-/CD34- CD73 CD45 45-/CD34- CD73 CD45 45-/CD34- CD271 Genomic analysis Frequent genomic gains: 1q31, 10q26 y 20q13 MSC are already abnormal before the culture process CD271 CD271 FISH confirmed BAC RP L1111 7p13 López-Villar et al, Leukemia 2009
15 Genes differently expressed by 5q- CGH arrays Unsupervised analysis Chr Genes 1p36.33 TNFRSF18;TNFRSF4 2p25.1 ID2 2p25.1 7p22.1 PDGF ; IEF2AK1 7p22.3 NUDT1 8q q12.2 MS4A3 11q13.1 FGF4; PRDX5 16p13.3 IL-32; TRAF7 16q q p11.2 RASD1 17q q25.1 CD300A 17q25.3 EPR1; BIRC5 19p13.11 GDF15 19p p q q13.41 KLK6-14 Angiogenesis Thrombopoiesis Apoptosis Hb synthesis 20q13 RASSF2A 21q q22.3
16 RT-PCR PCR: Overexpression in 5q- Thrombopoiesis Angiogenesis p>0.05 p>0.05 p=0.032 p=0.027 p=0.010 p>0.05 FGF4 Controls 5q- Non5q- Controls 5q- Non 5q- p=0.012 p>0.05 TNF p=0.007 p>0.05 p=0.010 p=0.032 IL32 PDGF Apoptosis Controls 5q- Non 5q- Controls 5q- Non 5q-
17 5q- Pathophysyology Mir145, mir146: Thrombocytosis Mir145, mir146 SPARC: Clonal advantage for HPC? H P C Platelets Adhesion molecules cytokines Erythrocytes Altered stromal function Adhesion? Cytokines? BM stromal cell RPS14: Erythroid expansion Apoptosis J ar d Apoptosis
18 5q- Pathophysyology Mir145, mir146: Thrombocytosis Mir145, mir146 SPARC: Clonal advantage for HPC? H P C Platelets Adhesion molecules FGF4 IL32 Erythrocytes Altered stromal function Adhesion? Cytokines? BM stromal cell RPS14: Erythroid expansion Apoptosis Apoptosis
19 Deletion of Dicer1 specifically in mouse osteoprogenitors disrupts the integrity of haematopoiesis. Therefore, perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced induced oncogenesis.
20 Universidad de Salamanca
Meeting Report. From December 8 to 11, 2012 at Atlanta, GA, U.S.A
Meeting Report Affiliation Department of Transfusion Medicine and Cell Therapy Name Hisayuki Yao Name of the meeting Period and venue Type of your presentation Title of your presentation The 54 th Annual
More informationMyelodysplastic Syndromes: Hematopathology. Analysis of SHIP1 as a potential biomarker of Disease Progression
Myelodysplastic Syndromes: Hematopathology. Analysis of SHIP1 as a potential biomarker of Disease Progression Carlos E. Bueso-Ramos, M.D., Ph.D Department of Hematopathology The University of Texas M.
More informationDISCLOSURE. I have the following financial relationships:
DISCLOSURE I have the following financial relationships: Consultant for: Fate Therapeutics, GlaxoSmithKline, Bone Therapeutics, G1 Therapeutics Contracted Research for: GlaxoSmithKline Royalties from:
More informationCD34+ Cells: A Comparison of Stem and Progenitor Cells in Cord Blood, Peripheral Blood, and the Bone Marrow
White Paper September 2016 CD34+ Cells: A Comparison of Stem and Progenitor Cells in Cord Blood, Peripheral Blood, and the Bone Marrow Lily C. Trajman, PhD Introduction: Hematopoietic Stem Cells (HSCs)
More informationCytokines, adhesion molecules and apoptosis markers. A comprehensive product line for human and veterinary ELISAs
Cytokines, adhesion molecules and apoptosis markers A comprehensive product line for human and veterinary ELISAs IBL International s cytokine product line... is extremely comprehensive. The assays are
More informationHematopoiesis. BHS Liège 27/1/2012. Dr Sonet Anne UCL Mont-Godinne
Hematopoiesis BHS Liège 27/1/2012 Dr Sonet Anne UCL Mont-Godinne Hematopoiesis: definition = all the phenomenons to produce blood cells Leukocytes = White Blood Cells Polynuclear = Granulocytes Platelet
More informationMyelodysplastic scoring system with flow cytometry. G Detry B Husson
Myelodysplastic scoring system with flow cytometry G Detry B Husson Myelodysplastic syndroms Clonal haematopoietic stem cell disease characterized by dysplasia in one or more of the myeloid cell lines
More informationAccelerate Your Research with Conversant Bio
Accelerate Your Research with Conversant Bio 400+ Participating MDs 50+ Partner sites for tissue procurement Continuous expansion of sourcing capabilities Closely monitored chain of custody Full regulatory
More informationACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT
ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes
More informationHematology Unit Lab 2 Review Material
Objectives Hematology Unit Lab 2 Review Material - 2018 Laboratory Instructors: 1. Assist students during lab session Students: 1. Review the introductory material 2. Study the case histories provided
More informationBasis of Immunology and
Basis of Immunology and Immunophysiopathology of Infectious Diseases Jointly organized by Institut Pasteur in Ho Chi Minh City and Institut Pasteur with kind support from ANRS & Université Pierre et Marie
More informationDISCOVERING ATCC IMMUNOLOGICAL CELLS - MODEL SYSTEMS TO STUDY THE IMMUNE AND CARDIOVASCULAR SYSTEMS
DISCOVERING ATCC IMMUNOLOGICAL CELLS - MODEL SYSTEMS TO STUDY THE IMMUNE AND CARDIOVASCULAR SYSTEMS James Clinton, Ph.D. Scientist, ATCC February 19, 2015 About ATCC Founded in 1925, ATCC is a non-profit
More informationHematology 101. Blanche P Alter, MD, MPH, FAAP Clinical Genetics Branch Division of Cancer Epidemiology and Genetics Bethesda, MD
Hematology 101 Blanche P Alter, MD, MPH, FAAP Clinical Genetics Branch Division of Cancer Epidemiology and Genetics Bethesda, MD Hematocrits Plasma White cells Red cells Normal, Hemorrhage, IDA, Leukemia,
More informationHaematopoietic stem cells
Haematopoietic stem cells Neil P. Rodrigues, DPhil NIH Centre for Biomedical Research Excellence in Stem Cell Biology Boston University School of Medicine neil.rodrigues@imm.ox.ac.uk Haematopoiesis: An
More informationCLINICAL USE OF CELLULAR SUBPOPULATION ANALYSIS IN BM
CLINICAL USE OF CELLULAR SUBPOPULATION ANALYSIS IN BM CANCER RESEARCH CENTRE, UNIVERSITY AND UNIVERSITY HOSPITAL OF SALAMANCA (SPAIN)( Sao Paulo, 18th of April, 2009 IDENTIFICATION OF HPC (I) 1.- In vivo
More informationGetting to the root of Cancer
Cancer Stem Cells: Getting to the root of Cancer Dominique Bonnet, Ph.D Senior Group Leader, Haematopoietic Stem Cell Laboratory Cancer Research UK, London Research Institute Venice, Sept 2009 Overview
More informationThe Role of Rac Signaling in The Perivascular Niche
The Role of Rac Signaling in The Perivascular Niche Felicia Ciuculescu Diaspora and Higher Education and Research Perspectives in Personalized Medicine- from Concept to Clinical Application Center for
More informationHeme 9 Myeloid neoplasms
Heme 9 Myeloid neoplasms The minimum number of blasts to diagnose acute myeloid leukemia is 5% 10% 20% 50% 80% AML with the best prognosis is AML with recurrent cytogenetic abnormality AML with myelodysplasia
More informationTissue renewal and Repair. Nisamanee Charoenchon, PhD Department of Pathobiology, Faculty of Science
Tissue renewal and Repair Nisamanee Charoenchon, PhD Email: nisamanee.cha@mahidol.ac.th Department of Pathobiology, Faculty of Science Topic Objectives 1. Describe processes of tissue repair, regeneration
More informationASH 2011 aktualijos: MSC TPŠL gydyme. Mindaugas Stoškus VULSK HOTC MRMS
ASH 2011 aktualijos: MSC TPŠL gydyme Mindaugas Stoškus VULSK HOTC MRMS #3042. Yukiyasu Ozawa et al. Mesenchymal Stem Cells As a Treatment for Steroid-Resistant Acute Graft Versus Host Disease (agvhd);
More informationCD90 + Human Dermal Stromal Cells Are Potent Inducers of FoxP3 + Regulatory T Cells
CD90 + Human Dermal Stromal Cells Are Potent Inducers of FoxP3 + Regulatory T Cells Karin Pfisterer, Karoline M Lipnik, Erhard Hofer and Adelheid Elbe-Bürger Journal of Investigative Dermatology (2015)
More informationMyelodysplastic Syndromes: Everyday Challenges and Pitfalls
Myelodysplastic Syndromes: Everyday Challenges and Pitfalls Kathryn Foucar, MD kfoucar@salud.unm.edu Henry Moon lecture May 2007 Outline Definition Conceptual overview; pathophysiologic mechanisms Incidence,
More informationCYTOKINES. Based on: Cellular and Molecular Immunology, 4 th ed.,abbas A.K., Lichtman A.H. and Pober J.S. Sounders company; Philadelphia, 2010.
CYTOKINES Based on: Cellular and Molecular Immunology, 4 th ed.,abbas A.K., Lichtman A.H. and Pober J.S. Sounders company; Philadelphia, 2010. 1 What are cytokines? Glycoproteins (15 25 kda): Interleukins
More informationNature Immunology: doi: /ni.3412
Supplementary Figure 1 Gata1 expression in heamatopoietic stem and progenitor populations. (a) Unsupervised clustering according to 100 top variable genes across single pre-gm cells. The two main cell
More informationBases for Immunotherapy in Multiple Myeloma
Bases for Immunotherapy in Multiple Myeloma Paola Neri, MD, PhD Associate Professor of Medicine University of Calgary, Arnie Charbonneau Cancer Institute Disclosures Paola Neri MD, PhD Grants/research
More informationMesenchymal Stem Cells
Mesenchymal Stem Cells Science and therapeutic applications Dirk Büscher (Former VP-R&D Cellerix) GRIFOLS SA May 10 th, 2010 EMA 1 Discovery and Definition of Mesenchymal Stem Cells MSC must be plastic-adherent
More informationNatural Killer Cells: Development, Diversity, and Applications to Human Disease Dr. Michael A. Caligiuri
Natural Killer Cells: Development, Diversity, November 26, 2008 The Ohio State University Comprehensive Cancer Center The James Cancer Hospital and Solove Research Institute Columbus, Ohio, USA 1 Human
More informationLymphoid architecture & Leukocyte recirculation. Thursday Jan 26th, 2017
Lymphoid architecture & Leukocyte recirculation Thursday Jan 26th, 2017 Topics The life of immune cells Where are they born? Where are they educated? Where do they function? How do they get there? The
More informationMATERIALS AND METHODS. Neutralizing antibodies specific to mouse Dll1, Dll4, J1 and J2 were prepared as described. 1,2 All
MATERIALS AND METHODS Antibodies (Abs), flow cytometry analysis and cell lines Neutralizing antibodies specific to mouse Dll1, Dll4, J1 and J2 were prepared as described. 1,2 All other antibodies used
More informationThe Immune System. A macrophage. ! Functions of the Immune System. ! Types of Immune Responses. ! Organization of the Immune System
The Immune System! Functions of the Immune System! Types of Immune Responses! Organization of the Immune System! Innate Defense Mechanisms! Acquired Defense Mechanisms! Applied Immunology A macrophage
More informationBasic Immunology. Cytokines, cytokine receptors. Lecture 8th. Timea Berki MD, PhD
Basic Immunology Lecture 8th Cytokines, cytokine receptors Timea Berki MD, PhD 1. By direct cell-cell interactions: through adhesion molecules 2. By low MW regulatory proteins, called cytokines: messengers
More informationTargeting tumour associated macrophages in anti-cancer therapies. Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018
Targeting tumour associated macrophages in anti-cancer therapies Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018 Macrophages: Professional phagocytes of the myeloid lineage APC,
More informationMyeloid neoplasms. Early arrest in the blast cell or immature cell "we call it acute leukemia" Myoid neoplasm divided in to 3 major categories:
Myeloid neoplasms Note: Early arrest in the blast cell or immature cell "we call it acute leukemia" Myoid neoplasm divided in to 3 major categories: 1. AML : Acute myeloid leukemia(stem cell with myeloid
More informationMYELODYSPLASTIC SYNDROMES: A diagnosis often missed
MYELODYSPLASTIC SYNDROMES: A diagnosis often missed D R. EMMA W YPKEMA C O N S U LTA N T H A E M AT O L O G I S T L A N C E T L A B O R AT O R I E S THE MYELODYSPLASTIC SYNDROMES DEFINITION The Myelodysplastic
More informationACCME/Disclosures 4/13/2016. Clinical History
ACCME/Disclosures The USCAP requires that anyone in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner
More informationAdaptive immune responses: T cell-mediated immunity
MICR2209 Adaptive immune responses: T cell-mediated immunity Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will discuss the T-cell mediated immune response, how it is activated,
More informationAbnormalities of the Immune System and Inflammation in MDS Pathogenesis. Shahram Kordasti MSc(Med Imm), MD, PhD Department of Haematological Medicine
Abnormalities of the Immune System and Inflammation in MDS Pathogenesis Shahram Kordasti MSc(Med Imm), MD, PhD Department of Haematological Medicine What is the role of immune system in MDS? Oligoclonal
More informationCorrespondence should be addressed to Anas Khanfar;
Case Reports in Oncological Medicine, Article ID 949515, 4 pages http://dx.doi.org/10.1155/2014/949515 Case Report Durable Hematological and Major Cytogenetic Response in a Patient with Isolated 20q Deletion
More informationMesenchymal Stem Cells to Repair Vascular Damage after Chemotherapy: Past, Present and Future
Mesenchymal Stem Cells to Repair Vascular Damage after Chemotherapy: Past, Present and Future Cell Therapy 2014 Las Vegas, NV, USA Sulaiman Al-Hashmi, PhD Sultan Qaboos University Oman What are MSCs? Stem
More informationCytokine Arrays Reveal Black Ops Tactics of Tumor-induced Immunosuppression
Cytokine Arrays Reveal Black Ops Tactics of Tumor-induced Immunosuppression Jarad J Wilson, Ph.D. Technical Support & Marketing Specialist Ruo-Pan Huang, MD, Ph.D. Founder and CEO What are Antibody Arrays?
More informationMDS FDA-approved Drugs
MDS: Current Thinking on the Disease, Diagnosis, and Treatment Mikkael A. Sekeres, MD, MS Associate Professor of Medicine Director, Leukemia Program Dept of Hematologic Oncology and Blood Disorders Taussig
More informationSupervisor: Prof. Dr. P Vandenberghe Dr. C Brusselmans
Contribution of molecular diagnosis in eosinophilia/hypereosinophilia Eosinophilia Hypereosinophilia Hypereosinophilic syndrome Immune mediated hypereosinophilia Chronic eosinophilic leukemia (NOS)/ Idiopathic
More informationSH/EAHP WORKSHOP 2017 CASE 210 PRESENTATION
SH/EAHP WORKSHOP 2017 CASE 210 PRESENTATION Jonathon H Gralewski DO, MS, Ginell R Post MD, PhD, Youzhong Yuan MD September 9, 2017 Clinical History 60 year old male with history of c-maf high-risk IgG
More informationNormal & Leukaemic haematopoiesis. Dr. Liu Te Chih Dept of Haematology / Oncology National University Health Services Singapore
Normal & Leukaemic haematopoiesis 2010 Dr. Liu Te Chih Dept of Haematology / Oncology National University Health Services Singapore Use of Immunophenotyping today Lineage assignment Differentiation of
More informationThe Role of Microenvironment in the Control of Tumor Angiogenesis
The Role of Microenvironment in the Control of Tumor Angiogenesis Domenico Ribatti The Role of Microenvironment in the Control of Tumor Angiogenesis Domenico Ribatti Department of Basic Medical Sciences,
More informationChronic Myeloid Leukemia Outlook: The Future of CML Therapy
Chronic Myeloid Leukemia Outlook: The Future of CML Therapy Neil Shah, MD PhD Edward S. AgenoDistinguished Professor in Hematology/Oncology UCSF School of Medicine San Francisco, California Progression
More informationHighly Efficient CRISPR/Cas9 Gene Editing and Long-Term Engraftment of Human Hematopoietic Stem and Progenitor Cells
Highly Efficient CRISPR/Cas9 Gene Editing and Long-Term Engraftment of Human Hematopoietic Stem and Progenitor Cells J. M. Heath, A. Chalishazar, C.S. Lee, W. Selleck, C. Cotta-Ramusino, D. Bumcrot, J.L.
More informationSeptember 20, Submitted electronically to: Cc: To Whom It May Concern:
History Study (NOT-HL-12-147), p. 1 September 20, 2012 Re: Request for Information (RFI): Building a National Resource to Study Myelodysplastic Syndromes (MDS) The MDS Cohort Natural History Study (NOT-HL-12-147).
More informationMyeloproliferative Disorders - D Savage - 9 Jan 2002
Disease Usual phenotype acute leukemia precursor chronic leukemia low grade lymphoma myeloma differentiated Total WBC > 60 leukemoid reaction acute leukemia Blast Pro Myel Meta Band Seg Lymph 0 0 0 2
More informationScientific report: Delineating cellular stages and regulation of human NK cell development to improve NK cell-based therapy for cancer (Dnr )
Scientific report: Delineating cellular stages and regulation of human NK cell development to improve NK cell-based therapy for cancer (Dnr 130259) The main goal of this project focuses on establishing
More informationMolecular Markers. Marcie Riches, MD, MS Associate Professor University of North Carolina Scientific Director, Infection and Immune Reconstitution WC
Molecular Markers Marcie Riches, MD, MS Associate Professor University of North Carolina Scientific Director, Infection and Immune Reconstitution WC Overview Testing methods Rationale for molecular testing
More informationThe Hierarchical Organization of Normal and Malignant Hematopoiesis
The Hierarchical Organization of Normal and Malignant Hematopoiesis NORMAL Hematopoie2c Stem Cell (HSC) Leukemia Stem Cells (LSC) MPP MLP CMP Leukemic Progenitors MEP GMP B/NK ETP Leukemic Blasts Erythrocytes
More informationShiv Pillai Ragon Institute, Massachusetts General Hospital Harvard Medical School
CTLs, Natural Killers and NKTs 1 Shiv Pillai Ragon Institute, Massachusetts General Hospital Harvard Medical School CTL inducing tumor apoptosis 3 Lecture outline CD8 + Cytotoxic T lymphocytes (CTL) Activation/differentiation
More informationMDS 101. What is bone marrow? Myelodysplastic Syndrome: Let s build a definition. Dysplastic? Syndrome? 5/22/2014. What does bone marrow do?
101 May 17, 2014 Myelodysplastic Syndrome: Let s build a definition Myelo bone marrow Gail J. Roboz, M.D. Director, Leukemia Program Associate Professor of Medicine What is bone marrow? What does bone
More informationThe Bone Marrow Stroma in Myeloproliferative Neoplasms. Dr Bridget S Wilkins Consultant Haematopathologist St Thomas Hospital, London
The Bone Marrow Stroma in Myeloproliferative Neoplasms Dr Bridget S Wilkins Consultant Haematopathologist St Thomas Hospital, London Normal BM Stromal Components - - Cells - - Mesenchymal origin: Adipocytes
More informationJournal Club WS 2012/13 Stefanie Nickl
Journal Club WS 2012/13 Stefanie Nickl Background Mesenchymal Stem Cells First isolation from bone marrow 30 ys ago Isolation from: spleen, heart, skeletal muscle, synovium, amniotic fluid, dental pulp,
More informationStem cells are undifferentiated cells which are maintained within a specific niche. A stem cell
Abstract Stem cells are undifferentiated cells which are maintained within a specific niche. A stem cell niche is a microenvironment of cells that maintain stem cell functionality, and one example is the
More informationBetter Prognosis for Patients With Del(7q) Than for Patients With Monosomy 7 in Myelodysplastic Syndrome
Better Prognosis for Patients With Del(7q) Than for Patients With Monosomy 7 in Myelodysplastic Syndrome Iris Cordoba, MD 1 ; José R. González-Porras, MD 1 ; Benet Nomdedeu, MD 2 ; Elisa Luño, MD 3 ; Raquel
More informationStem cells: units of development and regeneration. Fernando D. Camargo Ph.D. Whitehead Fellow Whitehead Institute for Biomedical Research.
Stem cells: units of development and regeneration Fernando D. Camargo Ph.D. Whitehead Fellow Whitehead Institute for Biomedical Research Concepts 1. Embryonic vs. adult stem cells 2. Hematopoietic stem
More informationFLOW CYTOMETRIC ANALYSIS OF NORMAL BONE MARROW
XI International Conference Hematopoiesis Immunology Budapest, June 6-7, 2014 FLO CYTOMETRIC ANALYSIS OF NORMAL BONE MARRO Bruno Brando and Arianna Gatti Hematology Laboratory and Transfusion Center Legnano
More informationin MDS Amit Verma Albert Einstein College of Medicine
Signal Transduction Inhibitors in MDS Amit Verma Albert Einstein College of Medicine Ineffective Hematopoiesis in MDS Hypercellular marrows with decreased peripheral blood counts Increased Cell death (Apoptosis/Cell
More informationstem cell products Basement Membrane Matrix Products Rat Mesenchymal Stem Cell Growth and Differentiation Products
stem cell products Basement Membrane Matrix Products Rat Mesenchymal Stem Cell Growth and Differentiation Products Stem Cell Qualified Extracellular Matrix Proteins Stem cell research requires the finest
More informationCan we classify cancer using cell signaling?
Can we classify cancer using cell signaling? Central hypotheses (big ideas) Alterations to signaling genes would cause leukemic cells to react in an inappropriate or sensitized manner to environmental
More informationBlood 101 Introduction Blood and Marrow & Overview of Bone Marrow Failure Diseases. Dr. M. Sabloff October 16 th 2010
Blood 101 Introduction Blood and Marrow & Overview of Bone Marrow Failure Diseases Dr. M. Sabloff October 16 th 2010 Normal Marrow knee joint white is articular cartilage Adjacent to this is the red marrow
More informationDefensive mechanisms include :
Acquired Immunity Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated immunity Humoral immunity Two mechanisms 1) Humoral
More informationCancer Biometrics: Results of the 2003 isbtc Workshop. Theresa L. Whiteside, Ph.D., ABMLI University of Pittsburgh Cancer Institute
Cancer Biometrics: Results of the 2003 isbtc Workshop Theresa L. Whiteside, Ph.D., ABMLI University of Pittsburgh Cancer Institute The workshop objective The objective was to consider state-of-theart approaches
More informationUMBILICAL CORD BLOOD STEM CELLS EXPANDED IN THE PRESENCE OF NICOTINAMIDE (NICORD) PROVIDE LONG TERM MULITI-LINEAGE ENGRAFTMENT
UMBILICAL CORD BLOOD STEM CELLS EXPANDED IN THE PRESENCE OF NICOTINAMIDE (NICORD) PROVIDE LONG TERM MULITI-LINEAGE ENGRAFTMENT Mitchell E. Horwitz, MD Duke University Medical Center Duke Cancer Institute
More informationChildhood hematopoiesis and hematological features. Yongmin Tang Dept. Hematology-oncology Chidlren s Hospital Zhejiang University School of medicine
Childhood hematopoiesis and hematological features Yongmin Tang Dept. Hematology-oncology Chidlren s Hospital Zhejiang University School of medicine Questions: How much have you known about our hematopoietic
More informationStem cells in endometriosis: pathogenetic factors and target for new medical treatments? Alberto Revelli MD PhD
Stem cells in endometriosis: pathogenetic factors and target for new medical treatments? Alberto Revelli MD PhD Gyn/Obst 1U, Physiopathology of Reproduction and IVF Unit Dept. Surgical Sciences, S. Anna
More informationClassification of Hematologic Malignancies. Patricia Aoun MD MPH
Classification of Hematologic Malignancies Patricia Aoun MD MPH Objectives Know the basic principles of the current classification system for hematopoietic and lymphoid malignancies Understand the differences
More informationSTEM CELLS. Dr Mohammad Ashfaq Konchwalla Consultant Orthopaedic Sports Surgeon
STEM CELLS Dr Mohammad Ashfaq Konchwalla Consultant Orthopaedic Sports Surgeon www.dubaisportssurgery.com PRACTICE SAUDI GERMAN HOSPITAL, DUBAI MEDCARE HOSPITAL, DUBAI Totipotent cells are cells that can
More information12 Dynamic Interactions between Hematopoietic Stem and Progenitor Cells and the Bone Marrow: Current Biology of Stem Cell Homing and Mobilization
Table of Contents: PART I: Molecular and Cellular Basis of Hematology 1 Anatomy and Pathophysiology of the Gene 2 Genomic Approaches to Hematology 3 Regulation of Gene Expression, Transcription, Splicing,
More informationThe hematopoiesis-supporting function of bone marrow stroma cells in patients with hematological malignancies
Medizinische Fakultät der Universität Duisburg-Essen Zentrum für Innere Medizin Klinik für Hämatologie The hematopoiesis-supporting function of bone marrow stroma cells in patients with hematological malignancies
More informationPNH Glossary of Terms
AA Absolute neutrophil count Alendronate Allergen ALT Anemia Antibodies Anticoagulant Anticoagulation Antigen Antithymocyte globulin (ATG) Aplastic Aplastic anemia Band Bilirubin Blast cells Bone marrow
More informationA prospective, multicenter European Registry for newly diagnosed patients with Myelodysplastic Syndromes of IPSS low and intermediate-1 subtypes.
Protocol Synopsis Study Title A prospective, multicenter European Registry for newly diagnosed patients with Myelodysplastic Syndromes of IPSS low and intermediate-1 subtypes. Short Title European MDS
More informationHEMATOLOGIC MALIGNANCIES BIOLOGY
HEMATOLOGIC MALIGNANCIES BIOLOGY Failure of terminal differentiation Failure of differentiated cells to undergo apoptosis Failure to control growth Neoplastic stem cell FAILURE OF TERMINAL DIFFERENTIATION
More informationLENALIDOMIDA EN EL SMD 5Q-
LENALIDOMIDA EN EL SMD 5Q- EXPERIENCIA ESPAÑOLA 37 Diada Internacional 7 de Junio de 2013 M. Díez Campelo Hematología HOSPITAL UNIVERSITARIO 15-30% MDS Introduction Sole anomaly or in addition to 1 cytogenetics
More informationDeregulated Genes in Hematopoietic Stem Cells Isolated from Spleen of Patients with Myelofibrosis
Abstract #96285 Deregulated Genes in Hematopoietic Stem Cells Isolated from Spleen of Patients with Myelofibrosis Paolo Catarsi 1*, Francesca Cordero 2*, Giulio Ferrero 2*, Marco Beccuti 2*, Valentina
More informationNiCord Single Unit Expanded Umbilical Cord Blood Transplantation: Results of Phase I/II Trials
NiCord Single Unit Expanded Umbilical Cord Blood Transplantation: Results of Phase I/II Trials Mitchell E. Horwitz, MD Duke University Medical Center Duke Cancer Institute Adult Umbilical Cord Blood Transplantation
More information2 nd step do Bone Marrow Study If possible both the aspiration and
Blood Malignancies-I Prof. Herman Hariman,SpPK a (KH). Ph.D.(U.K) Prof. Dr. Adikoesoema Aman, SpPK (KH) Dept. Clinpath, FK-USU First do the Full Blood Count Hb, WBCS, Platelets Morphology!! Such as blasts,
More informationTopically Applicable Stromal Cell Growth Factors - Encapsulated Cosmeceuticals
Topically Applicable Stromal Cell Growth Factors - Encapsulated Cosmeceuticals Stem cells move to injured area, differentiate into neighboring cells, and replace the damaged cells Cell Eons Stem cells
More informationACCME/Disclosures. History. Hematopathology Specialty Conference Case #4 4/13/2016
Hematopathology Specialty Conference Case #4 Sherrie L. Perkins MD, PhD University of Utah ACCME/Disclosures The USCAP requires that anyone in a position to influence or control the content of CME disclose
More informationManagement of Myelodysplastic Syndromes
Management of Myelodysplastic Syndromes Peter L. Greenberg, MD Stanford Cancer Institute Myelodysplastic Syndromes: Clinical & Molecular Advances for Disease Classification and Prognostication MDSs: A
More informationMyelodysplastic syndrome - from bone marrow studies to new therapy
Myelodysplastic syndrome - from bone marrow studies to new therapy EAHP Uppsala 2010 Eva Hellström-Lindberg Karolinska Institutet, Stockholm, Sweden Dept of Hematology Karolinska University Hospital Disese
More informationThe Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D.
The Development of Lymphocytes: B Cell Development in the Bone Marrow & Peripheral Lymphoid Tissue Deborah A. Lebman, Ph.D. OBJECTIVES 1. To understand how ordered Ig gene rearrangements lead to the development
More informationPREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland
AD Award Number: W81XWH-13-1-0057 TITLE: Role of TIRAP in Myelodysplastic Syndromes PRINCIPAL INVESTIGATOR: Linda Ya-ting Chang CONTRACTING ORGANIZATION: British Columbia Cancer Agency Branch Vancouver,
More informationReview Article Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms
Mediators of Inflammation Volume 2015, Article ID 869242, 17 pages http://dx.doi.org/10.1155/2015/869242 Review Article Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms Gregor
More informationHealing & Repair. Tissue Regeneration
Healing & Repair Dr. Srikumar Chakravarthi Repair & Healing: Are they same? Repair :Regeneration of injured cells by cells of same type, as with regeneration of skin/oral mucosa (requires basement membrane)
More informationParacrine Mechanisms in Adult Stem Cell Signaling and Therapy
Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy Massimiliano Gnecchi, Zhiping Zhang, Aiguo Ni, Victor J. Dzau Circulation Research 2008 Nov 21;103(11):1204-19 Introduction(1) After AMI all
More informationWhat is MDS? Epidemiology, Diagnosis, Classification & Risk Stratification
What is MDS? Epidemiology, Diagnosis, Classification & Risk Stratification Rami Komrokji, MD Clinical Director Malignant Hematology Moffitt Cancer Center Normal Blood and Bone Marrow What is MDS Myelodysplastic
More information«Mice are not small people» A. Rangarajan & Weinberg R. Nature Reviews Cancer 3,
«Mice are not small people» A. Rangarajan & Weinberg R. Nature Reviews Cancer 3, 952-959. 2003. Most common age-related neoplasm Humans in the West = Epithelial * Basal-cell carcinoma of skin * Breast
More informationTARGETED THERAPY FOR CHILDHOOD CANCERS
TARGETED THERAPY FOR CHILDHOOD CANCERS AZIZA SHAD, MD AMEY DISTINGUISHED PROFESSOR OF PEDIATRIC HEMATOLOGY ONCOLOGY, BLOOD AND MARROW TRANSPLANTATION LOMBARDI CANCER CENTER GEORGETOWN UNIVERSITY HOSPITAL
More informationSupplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured
Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured under Th0, Th1, Th2, Th17, and Treg conditions. mrna
More informationCytokines modulate the functional activities of individual cells and tissues both under normal and pathologic conditions Interleukins,
Cytokines http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation the_immune_response.html Cytokines modulate the functional activities of individual cells and tissues both under
More informationImpaired expression of DICER, DROSHA, SBDS and some micrornas in mesenchymal stromal cells from myelodysplastic syndrome patients
ORIGINAL ARTICLES Impaired expression of DICER, DROSHA, SBDS and some micrornas in mesenchymal stromal cells from myelodysplastic syndrome patients Carlos Santamaría, 1,2,3 * Sandra Muntión, 1,2,3 * Beatriz
More informationnumber Done by Corrected by Doctor Maha Shomaf
number 19 Done by Waseem Abo-Obeida Corrected by Abdullah Zreiqat Doctor Maha Shomaf Carcinogenesis: the molecular basis of cancer. Non-lethal genetic damage lies at the heart of carcinogenesis and leads
More informationCytokines. Luděk Šefc. Cytokines Protein regulators of cellular communication. Cytokines x hormones
Cytokines Luděk Šefc Cytokines Protein regulators of cellular communication Cytokines x hormones Hormones Cytokines Production sites few many Cell targets few many Presence in blood yes rarely Biological
More informationGeneration of post-germinal centre myeloma plasma B cell.
Generation of post-germinal centre myeloma. DNA DAMAGE CXCR4 Homing to Lytic lesion activation CD38 CD138 CD56 Phenotypic markers Naive Secondary lymphoid organ Multiple myeloma is a malignancy of s caused
More informationTITLE: Assessing the Mechanisms of MDS and its Transformation to Leukemia in a Novel Humanized Mouse. REPORT DATE: September 2014
AWARD NUMBER: W81XWH-13-1-0245 TITLE: Assessing the Mechanisms of MDS and its Transformation to Leukemia in a Novel Humanized Mouse PRINCIPAL INVESTIGATOR: Stephanie Halene CONTRACTING ORGANIZATION: Yale
More information