scholarly journals Aggressive Periodontitis with Neutropenia Caused by MMD2 Mutation

2019 ◽  
Author(s):  
Noriyoshi Mizuno ◽  
Hiroyuki Morino ◽  
Keichiro Mihara ◽  
Tomoyuki Iwata ◽  
Yoshinori Ohno ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Aggressive Periodontitis ◽  
Immune Defense ◽  
Tissue Destruction ◽  
Gene Encoding ◽  
Japanese Family ◽  
Hematopoietic Stem ◽  
System Defect ◽  
Functionally Impaired ◽  
Stem And Progenitor Cells

AbstractAggressive periodontitis causes rapid periodontal tissue destruction and is a disease that occurs at a young age and runs in the patient’s family. Here, we revealed a heterozygous A116V missense mutation in the gene encoding monocyte to macrophage differentiation associated 2 (MMD2) protein in a Japanese family with aggressive periodontitis and neutropenia. Analyses of patients’ peripheral blood revealed a low number of neutrophils but abundant quantity of CD34+ hematopoietic stem and progenitor cells (HSPCs). Moreover, mutant Mmd2 mice showed severe alveolar bone loss and neutropenia. In patients and mutant Mmd2 mice, differentiation of HSPCs into granulocytes was also impeded, and their granulocytes were functionally impaired. Taken together, A116V mutation in MMD2 gene induced mild neutropenia and slightly limited the immune defense response. Our studies suggested that aggressive periodontitis in association with A116V MMD2 mutation constitutes a new immune system defect that belongs to the same spectrum of severe congenital neutropenia.

scholarly journals Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 303-313 ◽  
Author(s):  
Olga Bromberg ◽  
Benjamin J. Frisch ◽  
Jonathan M. Weber ◽  
Rebecca L. Porter ◽  
Roberto Civitelli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Rapid Expansion ◽  
Intermittent Treatment ◽  
Gene Encoding ◽  
Hematopoietic Stem ◽  
Targeted Deletion ◽  
Bone Phenotype ◽  
Age Dependent ◽  
Stem And Progenitor Cells

Abstract Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment. Controversy exists on N-cadherin's role in support of HSCs. Specifically, it is unknown whether microenvironmental N-cadherin is required for normal marrow microarchitecture and for hematopoiesis. To determine whether osteoblastic N-cadherin is required for HSC regulation, we used a genetic murine model in which deletion of Cdh2, the gene encoding N-cadherin, has been targeted to cells of the osteoblastic lineage. Targeted deletion of N-cadherin resulted in an age-dependent bone phenotype, ultimately characterized by decreased mineralized bone, but no difference in steady-state HSC numbers or function at any time tested, and normal recovery from myeloablative injury. Intermittent parathyroid hormone (PTH) treatment is well established as anabolic to bone and to increase marrow HSCs through microenvironmental interactions. Lack of osteoblastic N-cadherin did not block the bone anabolic or the HSC effects of PTH treatment. This report demonstrates that osteoblastic N-cadherin is not required for regulation of steady-state hematopoiesis, HSC response to myeloablation, or for rapid expansion of HSCs through intermittent treatment with PTH.

The molecular signature of MDS stem cells supports a stem-cell origin of 5q− myelodysplastic syndromes

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 3005-3014 ◽  
Author(s):  
Lars Nilsson ◽  
Patrik Edén ◽  
Eleonor Olsson ◽  
Robert Månsson ◽  
Ingbritt Åstrand-Grundström ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Myelodysplastic Syndromes ◽  
Global Gene Expression ◽  
Molecular Signature ◽  
Gene Encoding ◽  
Hematopoietic Stem ◽  
Altered Expression ◽  
Stem And Progenitor Cells ◽  
Global Gene Expression Profiling

Abstract Global gene expression profiling of highly purified 5q-deleted CD34+CD38−Thy1+ cells in 5q− myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38−Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q− stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.

Flow cytometric enumeration and immunophenotyping of hematopoietic stem and progenitor cells

2001 ◽  
Vol 38 (2) ◽  
pp. 139-147
Author(s):  
Jan W. Gratama ◽  
D. Robert Sutherland ◽  
Michael Keeney
Keyword(s):  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Flow Cytometric ◽  
Stem And Progenitor Cells

Detecting Human CD34 + and CD34 - Hematopoietic Stem and Progenitor Cells Using a Sysmex Automated Hematology Analyzer

2004 ◽  
Vol 10 (4) ◽  
pp. 200-205 ◽  
Author(s):  
F. S. WANG ◽  
R. M. ROWAN ◽  
M. CREER ◽  
A. HAY ◽  
M. DORFNER ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Human Cd34 ◽  
Hematology Analyzer ◽  
Stem And Progenitor Cells ◽  
Automated Hematology Analyzer

Identification of nucleotide substitution in gene encoding [LeuA3]insulin in third Japanese family

Diabetes ◽  
1988 ◽  
Vol 37 (8) ◽  
pp. 1068-1070 ◽  
Author(s):  
T. Awata ◽  
Y. Iwamoto ◽  
A. Matsuda ◽  
T. Kuzuya
Keyword(s):  
Nucleotide Substitution ◽  
Gene Encoding ◽  
Japanese Family

scholarly journals Periodontal Manifestations in a Patient with Haim-Munk Syndrome

2010 ◽  
Vol 04 (03) ◽  
pp. 338-340
Author(s):  
Kamile Erciyas ◽  
Serhat Inaloz ◽  
A. Fuat Erciyas
Keyword(s):  
Autosomal Recessive ◽  
Alveolar Bone ◽  
Bone Destruction ◽  
Autosomal Recessive Disorder ◽  
Aggressive Periodontitis ◽  
Pes Planus ◽  
Rare Autosomal Recessive Disorder ◽  
Rare Anomaly ◽  
Palmoplantar Hyperkeratosis

Haim-Munk syndrome is an extremely rare autosomal recessive disorder characterized clinically by palmoplantar hyperkeratosis, aggressive periodontitis with severe alveolar bone destruction, onychogryphosis, pes planus, arachnodactyly, and acro-osteolysis. Consanguinity seems a notable prerequisite. The aim of this study was therefore to report one case of this syndrome and to focus on the periodontal manifestations, in order to attract the attention of dental clinicians to this rare anomaly. (Eur J Dent 2010;4:338-340)

scholarly journals Myelopoiesis during Solid Cancers and Strategies for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 968
Author(s):  
Tyler J. Wildes ◽  
Bayli DiVita Dean ◽  
Catherine T. Flores
Keyword(s):  
Myeloid Cells ◽  
Hematopoietic Stem ◽  
Cell Therapies ◽  
Broad Array ◽  
Stem And Progenitor Cells ◽  
Recent Developments ◽  
Immature Myeloid Cells ◽  
Significant Discovery ◽  
The Relationship ◽  
Clinical Advances

Our understanding of the relationship between the immune system and cancers has undergone significant discovery recently. Immunotherapy with T cell therapies and checkpoint blockade has meaningfully changed the oncology landscape. While remarkable clinical advances in adaptive immunity are occurring, modulation of innate immunity has proven more difficult. The myeloid compartment, including macrophages, neutrophils, and dendritic cells, has a significant impact on the persistence or elimination of tumors. Myeloid cells, specifically in the tumor microenvironment, have direct contact with tumor tissue and coordinate with tumor-reactive T cells to either stimulate or antagonize cancer immunity. However, the myeloid compartment comprises a broad array of cells in various stages of development. In addition, hematopoietic stem and progenitor cells at various stages of myelopoiesis in distant sites undergo significant modulation by tumors. Understanding how tumors exert their influence on myeloid progenitors is critical to making clinically meaningful improvements in these pathways. Therefore, this review will cover recent developments in our understanding of how solid tumors modulate myelopoiesis to promote the formation of pro-tumor immature myeloid cells. Then, it will cover some of the potential avenues for capitalizing on these mechanisms to generate antitumor immunity.

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