Myeloproliferative Neoplasms, An Issue of Hematology/Oncology Clinics of North America

1st Edition, Volume 35-2 - February 27, 2021
Editors: John Mascarenhas, Ronald Hoffman, Ross Levine, Raajit Rampal
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 7 9 5 8 8 - 3
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 7 9 5 8 9 - 0

This issue of Hematology/Oncology Clinics, guest edited by Drs. Ronald Hoffman, Ross Levine, John Mascarenhas, and Raajit Rampal, is dedicated to Myeloproliferative Neoplasms. This… Read more

Myeloproliferative Neoplasms, An Issue of Hematology/Oncology Clinics of North America

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This issue of Hematology/Oncology Clinics, guest edited by Drs. Ronald Hoffman, Ross Levine, John Mascarenhas, and Raajit Rampal, is dedicated to Myeloproliferative Neoplasms. This issue is one of six selected each year by the series consulting editors, Drs. George P. Canellos and Edward J. Benz. Topics in this issue include—but are not limited to— Overview of pathophysiology and potential drug targets, The role of the megakaryocyte, Epigenetics, Genetics, Novel technologies for understanding MPN biology, Important pathology considerations, Current Clinical investigations, Quality of life, Application of stem cell therapy, Immunotherapy approaches, Clinical unmet needs in ET/PV, Accelerated and blast phase MPNs, Epidemiology, Thrombotic and hemorrhagic complications, Murine modeling, The microenvironment in MPNs, MDS/MPN overlap syndrome, and Advancing effective clinical trial designs.

Cover image
Title page
Table of Contents
Copyright
Contributors
Forthcoming Issues
Preface
Overview of Myeloproliferative Neoplasms: History, Pathogenesis, Diagnostic Criteria, and Complications
Key points
Introduction
History
Diagnostic criteria
Pathogenesis
Complications
Summary
Clinics care points
Epidemiology of the Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms
Key points
Introduction
Etiology
Incidence
Prevalence
Survival
Summary
Clinics care points
The Role of Megakaryocytes in Myelofibrosis
Key points
Introduction
Background
Thrombopoietin signaling
JAK/STAT signaling
Megakaryocyte secretome
Inflammation
Summary
The Microenvironment in Myeloproliferative Neoplasms
Key points
Introduction
Chronic inflammation as a contributor to the development of myeloproliferative neoplasms
Myeloproliferative neoplasm subtype–specific cytokine signatures
Association of cytokines with specific disease outcomes
Cellular components of inflammation in myeloproliferative neoplasm
Looking ahead—how could we incorporate knowledge of the microenvironment to aid in the clinical care of patients with myeloproliferative neoplasm?
Genetics of Myeloproliferative Neoplasms
Key points
Background
Somatic driver mutations mediating constitutive JAK2-STAT activation
Somatic mutations in genes broadly affected in myeloid malignancies
Germline genetic factors involved in myeloproliferative neoplasms
Somatic driver mutations of myeloproliferative neoplasms in clonal hematopoiesis
Clinical significance of genetic markers in myeloproliferative neoplasms
Summary
Clinics care points
Epigenetic Dysregulation of Myeloproliferative Neoplasms
Key points
Introduction
Epigenetic dysfunction from aberrant JAK/STAT signaling
Co-occurring epigenetic modifying mutations in myeloproliferative neoplasms
Preclinical models of epigenetic modifying proteins in myeloproliferative neoplasms
Emerging epigenetic modifying therapies for the treatment of myelofibrosis
Summary
Clinics care point
Murine Modeling of Myeloproliferative Neoplasms
Key points
Introduction
Mouse modeling
JAK2
MPL and CALR
Preclinical testing
Epigenetic mutations
Signaling, transcription factor, and other mutations
Other myeloproliferative neoplasm disease models
Summary
Clinics care points
Important Pathologic Considerations for Establishing the Diagnosis of Myelofibrosis
Key points
Introduction
Discerning primary from secondary post–essential thrombocythemia and post–polycythemia vera myelofibrosis
Application of Single-Cell Approaches to Study Myeloproliferative Neoplasm Biology
Key points
Introduction
Single-cell genomics
Single-cell transcriptomics
Digital pathology
Summary
Financial support and sponsorship
Unmet Need in Essential Thrombocythemia and Polycythemia Vera
Key points
Introduction
Current state of treatment of essential thrombocytosis/polycythemia vera
Should we use low-dose aspirin in all patients with essential thrombocytosis and polycythemia vera?
Is there a target platelet count when using cytoreduction for essential thrombocytosis?
Do we have any medications that are truly disease-modifying?
What really is disease-modifying anyway?
Summary
Clinics care points
Thrombotic, Vascular, and Bleeding Complications of the Myeloproliferative Neoplasms
Key points
Introduction
Genomic profile and risk of thrombotic and vascular complications in the MPNs
Vascular disease and thrombosis in clonal hematopoiesis of indeterminate potential
Nongenomic risks of thrombotic and vascular complications in the myeloproliferative neoplasms
Venous thromboembolism in the myeloproliferative neoplasms
Arterial thrombosis and atherothrombosis in the myeloproliferative neoplasms
Microvascular complications in the myeloproliferative neoplasms
Bleeding complications in the myeloproliferative neoplasms
Pathobiology of thrombosis in the myeloproliferative neoplasms
Prevention and treatment of thrombotic, vascular, and bleeding complications in the myeloproliferative neoplasms
Future directions
Accelerated and Blast Phase Myeloproliferative Neoplasms
Key points
Introduction
Discussion
Summary
Clinics care points
Traipsing Through Muddy Waters: A Critical Review of the Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) Overlap Syndromes
Key points
Introduction
Historical perspective
Diagnostic considerations
Molecular characterization and management implications
Prognosis and risk stratification
Treatment Approach
Discussion and Future Directions
Summary
Clinics care points
Current Clinical Investigations in Myelofibrosis
Key points
Introduction
Overview of the pathobiology of myelofibrosis
Janus Associated Kinase inhibitors
Signal crosstalk-based monotherapy and combinatorial therapy
Epigenetic targeted therapies
Agents targeting the apoptotic pathway
Agents targeting the tumor microenvironment
Agents targeting cytokines/host immunity
Imetelstat
Agents targeted at mitigation of myelofibrosis-related cytopenias
Summary
Quality of Life in Myeloproliferative Neoplasms: Symptoms and Management Implications
Key points
Introduction
Measuring patient-reported outcomes in patients with myeloproliferative neoplasms
Biology of myeloproliferative neoplasm symptoms and inflammation, cytokines, and biology
Symptoms and JAK inhibition
Symptoms and cytoreduction
Symptoms, quality of life, and allogenic stem cell transplantation
Fatigue
Symptoms and drugs in the myeloproliferative neoplasm pipeline
Nonsymptom drivers of quality of life in patients with myeloproliferative neoplasms
Differences in treatment goals between patients with myeloproliferative neoplasms and providers
Quality of life and symptoms impact on treatment guidelines
Nonpharmacologic strategies for managing symptoms of myeloproliferative neoplasms
Summary
Clinics care points
Application of Stem Cell Therapy in Myelofibrosis
Key points
Background
Current expert guidance
Summary
Clinics care points
Disclaimer
Immunotherapy and Immunomodulation in Myeloproliferative Neoplasms
Key points
Introduction
Interferon-α
Immunomodulatory drugs
Immune checkpoint inhibitors
Cell-mediated immunotherapy and chimeric antigen receptor-modified T cells
Ruxolitinib: first-in-class JAK inhibitor, with a focus on immunomodulatory properties
Future directions: MPNs, inflammation, and novel agents with immune-modulating features
Discussion
Clinics care points
Advancing Effective Clinical Trial Designs for Myelofibrosis
Key points
Introduction
Phase I
Phase II
Phase III
Adaptive and other designs
Endpoints in myelofibrosis
Patient-reported outcomes
Myelofibrosis trials during the past decade
Summary
Clinics care points