scholarly journals Essential Thrombocythemia: Current Molecular and Therapeutic Insights

2015 ◽  
Vol 5 (1) ◽  
pp. 5-10
Author(s):  
Fatin M. Al-Sayes ◽  
Kalamegam Gauthaman
Keyword(s):  
Essential Thrombocythemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Disorders ◽  
Integrated Approach ◽  
Accurate Diagnosis ◽  
World Health ◽  
Systematic Analysis ◽  
Hematopoietic Stem ◽  
Health Organization

Essential thrombocythemia is one of the Philadelphia chromosome negative, clonal myeloproliferative disorders involving the hematopoietic stem cells and is characterized by elevated platelet counts and attendant thromboembolic phenomenon. A point mutation in the Janus-Activated Kinase 2 gene (JAK2V617F) accounts for nearly 50% of Essential thrombocythemia patients while about 10% have mutations in the thrombopoetin receptor (MPL) gene (MPLW515L/K). Several other genes are implicated, clearly indicating the existence of drivers both common and uncommon in the causation of Essential thrombocythemia. Genotyping for mutations will therefore be a useful diagnostic tool for detection of Janus-Activated Kinase 2 negative, MPL negative, Essential thrombocythemia patients. An integrated approach of systematic analysis leading to accurate diagnosis will enable risk stratification and institution of therapy following the World Health Organization guidelines. In addition to Janus-Activated Kinase inhibitors, a combination of agents that has anti-inflammatory properties could help prevention and/or reversal of fibrosis.

Myeloproliferative Neoplasms – Classification, Diagnostic and Therapeutic Options in the Light of Molecular Findings

2009 ◽  
Vol 03 (01) ◽  
pp. 57 ◽  
Author(s):  
Andrzej Hellmann ◽  
Maria Bieniaszewska ◽  
◽  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Myeloproliferative Neoplasms ◽  
Target Therapy ◽  
Diagnostic Procedures ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Lymphoid Tissues ◽  
Health Organization ◽  
Molecular Aberrations

The discovery of specific molecular aberrations (gene fusions or mutations) has had a profound effect on the understanding and management of myeloproliferative disorders (MPDs). First, it has provided clear evidence that all of these disorders are of neoplastic origin. This fact resulted in the change of the nomenclature proposed in the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues 2008, where the term MPDs was replaced by myeloproliferative neoplasms (MPNs). Second, useful tools for diagnostic procedures were developed, i.e. polymerase chain reaction (PCR) or other molecular assays. Thanks to this, previous complicated diagnostic algorithms could be simplified and the numerical value requirements could be lowered, making the diagnosis simpler and quicker. The other implication of the molecular findings in myeloproliferative neoplasms is derived from the fact that all discovered mutations result in translation of proteins with tyrosine kinase activity. So, nowadays the majority of myeloproliferative neoplasms can be treated with target therapy using tyrosine kinase inhibitors.

Importance of genetic heterogeneity in curing adult acute leukemia (AL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. s1-s1
Author(s):  
Clara D. Bloomfield
Keyword(s):  
Kinase Inhibitors ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
World Health ◽  
High Dose ◽  
Molecular Heterogeneity ◽  
Cure Rate ◽  
Molecular Abnormalities ◽  
Health Organization

s1 Forty-five years ago adult AL was incurable. Since then we have discovered the striking heterogeneity of AL and its importance in selecting therapy, resulting in cure of increasing numbers of patients. Publication of the French-American-British classification 34 years ago resulted in acceptance that morphology and cytochemistry separated AL into two different diseases, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), that required separate treatment. During the next 15–20 years the importance of cytogenetics in dissecting ALL and AML into entities requiring different therapies became widely accepted, resulting in 2001 in their first incorporation into the World Health Organization (WHO) classification of AL. Over the last 10 years, discovery of molecular abnormalities within cytogenetic groups has further increased our ability to selectively treat and increasingly cure AL. The most striking example of increased curability of AL is acute promyelocytic leukemia, in which targeted therapy combined with chemotherapy has increased survival from a 2-week median to an 80% cure rate. Recognition of increased sensitivity of a genetic subtype of AML to high-dose cytarabine (HiDAC) has increased the cure rate of core-binding factor (CBF) AML from <10%–25% to 55%–60%. Recent discovery of the adverse impact of KIT mutations in CBF AML may allow the addition of tyrosine kinase inhibitors to HiDAC to substantially further increase cure. Among adult de novo AML 40%–45% are cytogenetically normal (CN); the striking molecular heterogeneity of CN-AML is now being recognized and promises to allow individualized approaches that improve substantially upon the current cure rate of 40%. In adult ALL the major adverse subgroup has a Philadelphia chromosome (PH+). New molecularly targeted approaches are allowing remissions in over 90% of PH+ elderly patients and appear likely to substantially cure an increasing fraction of younger PH+ adults. New approaches to studying the leukemia genome and epigenome should improve our understanding of AL heterogeneity, identify new therapeutic targets, and allow the cure of most patients.

scholarly journals A review of current knowledge of myeloproliferative disorders in the horse

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Chronic Granulocytic Leukemia ◽  
Current State ◽  
Multiple Cell ◽  
Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

scholarly journals An Unsuspected Finding of t(9;22): A Rare Case of Philadelphia Chromosome-Positive B-Lymphoblastic Lymphoma

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Prajwal Boddu ◽  
C. Cameron Yin ◽  
Rashmi Kanagal-Shamanna ◽  
Guillin Tang ◽  
Beenu Thakral ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
Philadelphia Chromosome ◽  
Lymphoblastic Lymphoma ◽  
Accurate Diagnosis ◽  
Biopsy Specimens ◽  
B Lymphoblastic Lymphoma ◽  
Prophylactic Chemotherapy

While rare, cases of isolated extramedullary disease of B-cell Lymphoblastic Lymphoma (B-LBL) without morphologic bone marrow involvement have been described. In this report, we illustrate the case of an elderly gentleman who presented with isolated testicular and vertebral LBL involvement but had no morphologic bone marrow involvement. The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence in situ hybridization (FISH) and PCR testing for BCR-ABL1 rearrangements were being performed on the marrow specimens as a part of routine diagnostic workup. While the FISH returned negative, PCR testing unexpectedly detected BCR-ABL1 fusion transcripts at a low level of 0.48%. Given their presence, we performed FISH for BCR/ABL1 rearrangement in both testicular and L5 vertebral specimens which were 80–90% positive. He subsequently received rituximab, hyper-CVAD, and dasatinib, along with prophylactic intrathecal prophylactic chemotherapy. The patient achieved a prolonged remission but eventually relapsed, 4 years later. Had it not been for this fortuitous discovery, the patient would not have been treated with tyrosine kinase inhibitors. We emphasize that FISH and PCR testing for BCR-ABL1 rearrangement are integral to arriving at an accurate diagnosis and should be routinely tested on B-LBL biopsy specimens.

scholarly journals An Innovative Approach to Designing Digital Health Solutions Addressing the Unmet Needs of Obese Patients in Europe

2021 ◽  
Vol 18 (2) ◽  
pp. 579
Author(s):  
Roberta Patalano ◽  
Vincenzo De Luca ◽  
Jess Vogt ◽  
Strahil Birov ◽  
Lucia Giovannelli ◽  
...  
Keyword(s):  
Unmet Needs ◽  
Negative Impact ◽  
Digital Health ◽  
Integrated Approach ◽  
World Health ◽  
Obese Patients ◽  
Unhealthy Lifestyle ◽  
Significant Negative Impact ◽  
Related Quality ◽  
Health Organization

According to the World Health Organization (WHO), the worldwide obesity rate has tripled since 1975. In Europe, more than half of the population is overweight and obese. Around 2.8 million people die each year worldwide as a result of conditions linked to being overweight or obese. This study aimed to analyze the policies, approaches, and solutions that address the social and health unmet needs of obese patients, at different levels, in order to simulate the definition of an integrated approach, and to provide and share examples of innovative solutions supporting health promotion, disease prevention, and integration of services to improve the collaboration between the different health and care stakeholders involved across the country and in the lives of obese patients. A collaborative approach involving various levels of government and regional experts from different European countries was applied to identify, explore, and evaluate different aspects of the topic, from the innovation perspective and focusing on a European and a regional vision. Currently, people prefer more foods rich in fats, sugars, and salt/sodium than fruits, vegetables, and fiber. This behavior leads to a significant negative impact on their health-related quality of life. Changes in healthcare systems, healthy policy, and approaches to patient care and better implementation of the different prevention strategies between all the stakeholders are needed, taking advantage of the digital transformation of health and care. Such changes can support obese patients in their fight against an unhealthy lifestyle and at the same time reduce healthcare costs.

scholarly journals IMPORTANCE OF CLASSICAL MORPHOLOGY IN THE DIAGNOSIS OF MYELODYSPLASTIC SYNDROME

2015 ◽  
Vol 7 ◽  
pp. e2015035 ◽  
Author(s):  
Rosangela Invernizzi ◽  
Federica Quaglia ◽  
Matteo Giovanni Della Porta
Keyword(s):  
Molecular Techniques ◽  
Classification Systems ◽  
World Health ◽  
Hematopoietic Stem ◽  
Morphological Alterations ◽  
Diagnosis And Classification ◽  
The Moment ◽  
Health Organization ◽  
Selection Of

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome  have necessitated the use of classification systems to improve diagnosis, prognostication and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and of peripheral blood cells are still fundamental for diagnostic classification. In this paper World Health Organization (WHO) classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although in the future morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders.

scholarly journals A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Paola Villafuerte-Gutiérrez ◽  
Montserrat López Rubio ◽  
Pilar Herrera ◽  
Eva Arranz
Keyword(s):  
Kinase Inhibitors ◽  
Fusion Gene ◽  
Myeloproliferative Neoplasms ◽  
Therapeutic Option ◽  
Myeloproliferative Neoplasm ◽  
Allogeneic Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Health Organization

Hematopoietic myeloproliferative neoplasms with FGFR1 rearrangement result in the 8p11 myeloproliferative syndrome that in the current Word Health Organization classification is designated as “myeloid and lymphoid neoplasm with FGFR1 abnormalities.” We report the case of a 66-year-old man who had clinical features that resembled chronic myeloid leukaemia (CML), but bone marrow cytogenetic and fluorescent in situ hybridization (FISH) studies showed t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. He was initially managed with hydroxyurea, and given the aggressive nature of this disease, four months later, the patient underwent an allogeneic hematopoietic stem-cell transplantation (HSCT) from an HLA-haploidentical relative. Currently, HSCT may be the only therapeutic option for long-term survival at least until more efficacious tyrosine kinase inhibitors (TKIs) become available.

Intimate partner violence

2018 ◽  
pp. 465-476
Author(s):  
Carmen Wong ◽  
Wai Ching Ng ◽  
Hua Zhong ◽  
Anne Scully-Hill
Keyword(s):  
Intimate Partner Violence ◽  
Partner Violence ◽  
Integrated Approach ◽  
Intimate Partner ◽  
World Health ◽  
Physical And Mental Health ◽  
Psychological Harm ◽  
And Gender ◽  
Health Organization ◽  
Internal And External Factors

Intimate partner violence (IPV) refers to any action that causes physical, sexual, and psychological harm by intimate partners, which includes domestic violence. This chapter gives a brief overview and details the prevalence, current theories, research, and evidence, including patriarchy and gender issues. IPV is complex, with internal and external factors relating to the victim, perpetrator, family, and the community. The long-term impacts on physical and mental health are reviewed. Recent direction by the World Health Organization describes a multi-level integrated approach, which is discussed topically in terms of individual, relational, and community prevention and intervention and its challenges. Finally, policies and laws relating to IPV are reviewed. This chapter has been written collaboratively by a multidisciplinary team of medical, social, and legal professionals.

scholarly journals A PTPmu Biomarker is Associated with Increased Survival in Gliomas

2019 ◽  
Vol 20 (10) ◽  
pp. 2372 ◽  
Author(s):  
Mette L. Johansen ◽  
Jason Vincent ◽  
Haley Gittleman ◽  
Sonya E. L. Craig ◽  
Marta Couce ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Integrated Approach ◽  
Tissue Microarrays ◽  
Adolescent And Young Adult ◽  
World Health ◽  
Lower Grade ◽  
Oligodendroglial Tumors ◽  
Molecular Approaches ◽  
Wide Range ◽  
Health Organization

An integrated approach has been adopted by the World Health Organization (WHO) for diagnosing brain tumors. This approach relies on the molecular characterization of biopsied tissue in conjunction with standard histology. Diffuse gliomas (grade II to grade IV malignant brain tumors) have a wide range in overall survival, from months for the worst cases of glioblastoma (GBM) to years for lower grade astrocytic and oligodendroglial tumors. We previously identified a change in the cell adhesion molecule PTPmu in brain tumors that results in the generation of proteolytic fragments. We developed agents to detect this cell surface-associated biomarker of the tumor microenvironment. In the current study, we evaluated the PTPmu biomarker in tissue microarrays and individual tumor samples of adolescent and young adult (n = 25) and adult (n = 69) glioma populations using a fluorescent histochemical reagent, SBK4-TR, that recognizes the PTPmu biomarker. We correlated staining with clinical data and found that high levels of the PTPmu biomarker correlate with increased survival of glioma patients, including those with GBM. Patients with high PTPmu live for 48 months on average, whereas PTPmu low patients live only 22 months. PTPmu high staining indicates a doubling of patient survival. Use of the agent to detect the PTPmu biomarker would allow differentiation of glioma patients with distinct survival outcomes and would complement current molecular approaches used in glioma prognosis.

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