Cellular and Molecular Aspects of Myeloproliferative Neoplasms - Part A (Volume 365) (International Review of Cell and Molecular Biology, Volume 365)

__Cellular and Molecular Aspects of Myeloproliferative Neoplasms - Part A, Volume 365__ in the __International Review of Cell and Molecular Biology__ series reviews and details current advances in cell and molecular biology. Chapters in this new release include MPN a continuum of different disease entities, Bone marrow microenvironment of MPN, Extramedullary hemopoiesis in MPN, The JAK2 mutation, Calreticulin mutations in myeloproliferative neoplasms, and Cytogenetic abnormalities and non-driver mutations in MPN. The IRCMB series has a worldwide readership, maintaining a high standard by publishing invited articles on important and timely topics that are authored by prominent cell and molecular biologists. The articles published in IRCMB have a high impact and an average cited half-life of 9 years. This great resource ranks high amongst scientific journals dealing with cell biology. Series-Page_2021_International-Review-of-Cell-and-Molecular-Biology Series Page Copyright_2021_International-Review-of-Cell-and-Molecular-Biology Copyright Contributors_2021_International-Review-of-Cell-and-Molecular-Biology Contributors Philadelphia-negative-myeloproliferative-neo_2021_International-Review-of-Ce Philadelphia-negative myeloproliferative neoplasms: From origins to new perspectives Acknowledgments Conflict of Interest References Chapter-One---Classical-Philadelphia-negative-myel_2021_International-Review Classical Philadelphia-negative myeloproliferative neoplasms (MPNs): A continuum of different disease entities Introduction Clinical characteristics of MPNs Constitutional symptoms Microvascular manifestations Thrombosis Bleeding Extramedullary hematopoiesis and splenomegaly Infections Disease progression Second primary malignancies Genetics of MPNs Driver mutations: JAK2, CALR and MPL Triple negative MPN Additional mutations in genes frequently involved in myeloid neoplasms Diagnostic criteria of MPNs Diagnostic criteria of PV Diagnostic criteria of ET Diagnostic criteria of PMF Diagnostic criteria of SMF Clinical and molecular-integrated prognostic scores in MPNs Prognostication in PV and ET Prognostication in primary and secondary MF Current standard treatment in MPNs Current standard treatment in PV Current standard treatment in ET Current standard treatment in primary and secondary MF Evolving therapies and clinical trials in MPNs Evolving therapies and clinical trials in primary and secondary MF Evolving therapies and clinical trials in PV Evolving therapies and clinical trials in ET Acknowledgments References Chapter-Two---Bone-marrow-microenviro_2021_International-Review-of-Cell-and- Bone marrow microenvironment of MPN cells Introduction The bone marrow niche in myeloproliferative neoplasms The hematopoietic compartment Hematopoietic stem cells Megakaryocytes Monocytes The vascular compartment The nervous compartment The stromal compartment The bone marrow extracellular matrix components in MPNs Prognostic significance of myelofibrosis The roles of extracellular matrices in MPN progression Collagens Fibronectins Thrombospondins Osteonectin Conclusions References Chapter-Three---Extramedullary-hematopoiesis-in-my_2021_International-Review Extramedullary hematopoiesis in myeloproliferative neoplasms: Pathophysiology and treatment strategies Introduction Extramedullary hematopoiesis Pathophysiology of EMH Therapeutic strategies JAK inhibitors Radiation and surgical intervention Hematopoietic stem cell transplant (HSCT) Non-JAK inhibitor pharmaceutical approaches Busulfan Hydroxyurea Thalidomide and lenalidomide Emerging research Conclusion Acknowledgments Conflict of interest References Chapter-Four---The-JAK2-muta_2021_International-Review-of-Cell-and-Molecular The JAK2 mutation JAK2: A non-receptor tyrosine kinase Structure and regulation of JAK2 Negative regulation of JAK2 Pathogenic activation of JAK2 JAK2 mutations in Ph-myeloproliferative neoplasms The JAK2V617F mutation: One mutation three phenotypes Essential thrombocythemia Polycythemia vera Primary myelofibrosis Natural evolution of JAK2V617F-positive MPNs: A continuum model JAK2 exon 12 mutations in PV Aberrant signaling downstream of JAK2V617F JAK-STAT5 pathway P13K/AKT pathway Ras/MAPK pathway Nuclear functions of JAK2V617F Effects of JAK2V617F on DNA damage and apoptosis Factors determining phenotypes in JAK2V617F-positive MPNs JAK2V617F allele burden Differential STAT signaling Host genetic factors Cellular effects of JAK2V617F Effects of JAK2V617F on hematopoietic progenitors Effects of JAK2V617F on hematopoietic stem cells Pre-JAK2V617F events JAK2V617F clonal diversity Concluding remarks References Chapter-Five---The-MPL-muta_2021_International-Review-of-Cell-and-Molecular- The MPL mutation Thrombopoietin receptor-MPL physiology MPL mutations in myeloproliferative neoplasms Clinical effect of MPL mutations in myeloproliferative neoplasms Conclusions References Chapter-Six---Calreticulin-mutations-in-m_2021_International-Review-of-Cell- Calreticulin mutations in myeloproliferative neoplasms Function of calreticulin CALR mutations Clinical features of CALR-mutant MPN Diagnostic significance Characteristics of CALR-mutant ET Characteristics of CALR-mutant PMF Differences depending on the type of mutation Differences in ET Differences in PMF Treatment of CALR-mutant MPN Treatment of ET Treatment of PMF and post-ET MF Molecular mechanism of MPL activation MPL-dependent transformation by mutant CALR Interaction between MPL and mutant CALR Mutant CALR binds to MPL MPL maturation and mutant CALR protein CALR oligomultimerization Significance of CALR localization changes due to mutation CALR mutation and disruption of intracellular homeostasis Changes in Ca signaling Effect on ER stress response Effects on stem cells and cell differentiation Analysis using human-derived stem cells Animal models (Table 3) Zebrafish models Bone marrow transplantation (BMT) models Transgenic (TG) mouse models Knock-in (KI) mouse models Frameshift (FS) mouse models at the endogenous Calr locus Insights from mouse models Disruption of the immune system Effect on antigen presentation Effect on danger signaling Treatment targeting mutant CALR protein Immunotherapy Small molecule inhibitors and peptide drugs Potential therapeutic targets Remaining questions Toward a breakthrough in MPN treatment References Cellular and Molecular Aspects of Myeloproliferative Neoplasms - Part A, Volume 365 in the International Review of Cell and Molecular Biology series reviews and details current advances in cell and molecular biology. Chapters in this new release include MPN a continuum of different disease entities, Bone marrow microenvironment of MPN, Extramedullary hemopoiesis in MPN, The JAK2 mutation, Calreticulin mutations in myeloproliferative neoplasms, and Cytogenetic abnormalities and non-driver mutations in MPN. The IRCMB series has a worldwide readership, maintaining a high standard by publishing invited articles on important and timely topics that are authored by prominent cell and molecular biologists. The articles published in IRCMB have a high impact and an average cited half-life of 9 years. This great resource ranks high amongst scientific journals dealing with cell biology. Publishes only invited review articles on selected topics Authored by established and active cell and molecular biologists and drawn from international sources Offers a wide range of perspectives on specific subjects