Abstract:
:Modern molecular technology helped identify more than 10 protein tyrosine kinases related to myeloid malignancies, which allowed the development of small molecule inhibitors targeting deregulated protein tyrosine kinase activity. Protein tyrosine kinase deregulation can occur as a consequence of fusion gene formation because of chromosomal translocations, or as distinct gain-of-function point mutations. Although the tyrosine kinase inhibitor imatinib mesylate (Gleevec) targeting the ABL protein tyrosine kinase has revolutionized current chronic myeloid leukemia therapy, it became rapidly evident that overcoming the multiple cellular resistance mechanisms will be very challenging. To develop efficient therapeutic alternatives, one must understand the complex signal transduction mechanisms involved in transformation by deregulated protein tyrosine kinases. This article reviews the most recently identified molecular mechanisms involved in cell transformation by the BCR/ABL protein tyrosine kinase fusion and presents new members of the increasing family of deregulated protein tyrosine kinases involved in myeloproliferative disorders. In addition, the article discusses new, promising small molecule protein tyrosine kinase inhibitors and the molecular mechanism that may lead to resistance to these drugs. Finally, the article highlights putative alternative strategies that could be used to block signal transduction pathways of deregulated protein tyrosine kinase activity.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Anastasiadou E,Schwaller Jdoi
10.1097/00062752-200301000-00007keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
40-8issue
1eissn
1065-6251issn
1531-7048journal_volume
10pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:The polycomb group gene BMI1 fulfills essential roles in both normal and leukemic stem cells. The underlying molecular mechanisms are beginning to become unraveled and an overview of the current knowledge on BMI1 signaling in normal and leukemic stem cells will be presented here. RECENT FINDINGS:In a...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e328338c439
更新日期:2010-07-01 00:00:00
abstract::Platelet glycoprotein (GP) IIb/IIIa receptor antagonists are being used with increasing frequency in the settings of percutaneous coronary interventions and acute ischemic syndromes. The development of bleeding complications following GPIIb/IIIa blockade represents a significant limitation to its effectiveness. Baseli...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199909000-00011
更新日期:1999-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Hemolytic anemias caused by premature destruction of red blood cells occur in many disorders including hemoglobinopathies, autoimmune conditions, during infection or following reaction to drugs or transfusions. Recent studies which will be reviewed here have uncovered several novel mechanisms by which...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000423
更新日期:2018-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Infantile hemangioma is a common vascular tumor with a unique lifecycle: rapid growth in infancy, followed by a period of involution, leading to complete regression. This review summarizes recent studies of molecular mechanisms of hemangioma formation and places new findings and hypotheses in the cont...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832a07ff
更新日期:2009-05-01 00:00:00
abstract:PURPOSE OF REVIEW:In addition to the crucial role of vascular endothelial growth factor (VEGF)A in vessel development, it has become apparent that the VEGF signaling pathway (VSP) plays an important role during adulthood in the maintenance of tissue homeostasis in normal physiological processes, as well as in pathologi...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32833865e6
更新日期:2010-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Iron homeostasis and erythropoiesis regulate each other to ensure optimal delivery of oxygen and iron to cells and tissues. Defining the mechanisms of this crosstalk is important for understanding the pathogenesis of common conditions associated with disordered iron metabolism and erythropoiesis. REC...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000132
更新日期:2015-05-01 00:00:00
abstract:PURPOSE OF REVIEW:To outline the rationale, limitations, and execution of bloodless medical and surgical programs, highlighting characteristics that contribute to successful outcomes. RECENT FINDINGS:Clinical experiences with patients who refuse blood transfusions for religious reasons have provided valuable lessons a...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000245692.32085.bd
更新日期:2006-11-01 00:00:00
abstract::Contrast venography remains the gold standard for the diagnosis of deep-vein thrombosis (DVT). However, an ongoing interest exists in developing safe diagnostic strategies that are less invasive, less expensive, widely and readily available, and more acceptable to patients than venography. For patients with symptoms s...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199909000-00001
更新日期:1999-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Chronic inflammation and disordered lipid metabolism represent hallmarks of atherosclerosis. Considerable evidence has accumulated to suggest that innate immune defense mechanisms might interact with proinflammatory pathways and exacerbate or perhaps even initiate development of arterial plaques. Unti...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000219662.88409.7c
更新日期:2006-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Fibroblast growth factor (FGF) signaling activates many bone marrow cell types, including various stem cells, osteoblasts, and osteoclasts. However, the role of FGF signaling in regulation of normal and leukemic stem cells is poorly understood. This review highlights the physiological roles of FGF sig...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283606162
更新日期:2013-05-01 00:00:00
abstract:PURPOSE OF REVIEW:The discovery of JAK2V617F and other JAK-STAT-activating mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPN) has led to the development of small-molecule ATP-mimetics that inhibit wild-type and mutant JAK. Here, we review the current experience with JAK inhibitors used for the treatment ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283439964
更新日期:2011-03-01 00:00:00
abstract::Disorders of the erythrocyte membrane, such as hereditary spherocytosis, hereditary elliptocytosis, and hereditary pyropoikilocytosis, are characterized by heterogeneity in their clinical and laboratory manifestations. Recent work has shown that these disorders also exhibit marked genetic heterogeneity. Multiple genet...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704020-00009
更新日期:1997-03-01 00:00:00
abstract::Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a transl...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200005000-00003
更新日期:2000-05-01 00:00:00
abstract:PURPOSE OF REVIEW:The role of bone morphogenetic proteins (BMPs) in vasculogenesis is still not well understood, despite many recent developments in this area of research. In this review, we discuss the most recent studies that identify new critical mechanisms through which BMP signaling acts with a focus on angiogenes...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832a07d6
更新日期:2009-05-01 00:00:00
abstract:PURPOSE OF THE REVIEW:Monitoring for residual leukemic burden is an integral part of ongoing evaluation in chronic myeloid leukemia. With high rates of complete cytogenetic response induced by imatinib and other tyrosine kinase inhibitors, exploring refinements in current methods of minimal residual disease monitoring ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282f42898
更新日期:2008-03-01 00:00:00
abstract::Human parvovirus B19 shows remarkable tropism for human erythroid progenitor cells. The pathogenesis of disease resulting from infection is a dynamic between the viral suppression of erythropoiesis and the host's ability to mount an effective immune response. Understanding this process has led to strategies for treati...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199603020-00002
更新日期:1996-03-01 00:00:00
abstract:PURPOSE OF REVIEW:The aim of this short study is to review recently published data bearing on how to resuscitate massive uncontrolled hemorrhage. RECENT FINDINGS:New data inform our understanding of the mechanisms of the acute coagulopathy of trauma, the median time to death of trauma patients with uncontrolled hemorr...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000184
更新日期:2015-11-01 00:00:00
abstract::Therapy with unconjugated monoclonal antibodies (mAbs) and radiolabeled mAbs has shown activity in patients with B-cell non-Hodgkin's lymphoma and leukemia. Drug-conjugated mAbs are active in relapsed leukemia. Using these new agents with and after chemotherapy induces a high rate of remission, but this needs to be co...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199907000-00005
更新日期:1999-07-01 00:00:00
abstract:PURPOSE OF REVIEW:The increasing use of high throughput sequencing and genomic analysis has facilitated the discovery of new causes of inherited platelet disorders. Studies of these disorders and their respective mouse models have been central to understanding their biology, and also in revealing new aspects of platele...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000525
更新日期:2019-09-01 00:00:00
abstract:PURPOSE OF REVIEW:This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction. RECENT FINDINGS:Autoantibodies are produced by a limited number...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282ba5552
更新日期:2007-09-01 00:00:00
abstract::Stem cell factor (SCF) is a multipotent growth factor that plays a role in the growth and development of hematopoietic cells, spermatocytes, melanocytes, and mast cells. SCF alone has little direct stimulatory activity on hematopoietic progenitors but acts synergistically with other colony-stimulating factors to poten...
journal_title:Current opinion in hematology
pub_type: 杂志文章
doi:10.1097/00062752-199704030-00001
更新日期:1997-05-01 00:00:00
abstract::Gene transfer has allowed a number of biologic issues in the therapy of hematologic malignancy to be addressed. In autologous bone marrow transplantation, gene marking studies have shown that infused marrow contributes to relapse in acute myeloid leukemia, neuroblastoma, and chronic myeloid leukemia. In addition, doub...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502060-00004
更新日期:1995-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Core binding factor acute myeloid leukemia (CBF-AML) corresponds to two distinct subtypes of AML characterized by recurrent favorable chromosome translocations, namely t(8;21) and inv(16)/t(16;16). Given the relatively good outcome of patients with CBF-AML, when treated with intensive chemotherapy inc...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283257b18
更新日期:2009-03-01 00:00:00
abstract::A variety of agents are available to improve hemostasis and reduce blood loss in multiple clinical settings. These agents are most commonly used to reduce bleeding when an underlying hemostatic defect is present. Some new agents offer the potential to decrease blood loss even in the absence of an obvious underlying he...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200211000-00014
更新日期:2002-11-01 00:00:00
abstract:PURPOSE OF REVIEW:In addition to its essential role in baseline erythropoiesis, the hormone erythropoietin drives the erythropoietic response to hypoxic stress. A mechanistic understanding of stress erythropoiesis would benefit multiple clinical settings, and may aid in understanding leukemogenesis. RECENT FINDINGS:Th...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3280de2bf1
更新日期:2007-05-01 00:00:00
abstract:PURPOSE OF REVIEW:The capacity of lithium to induce neutrophilia and increase circulating CD34(+) cells of marrow origin has long been known. Lithium has been the object of hematological investigations for many years, but no definitive use in hematology has yet emerged. RECENT FINDINGS:We review the evidence that lith...
journal_title:Current opinion in hematology
pub_type: 杂志文章,收录出版,评审
doi:10.1097/MOH.0b013e32834da93b
更新日期:2012-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Despite parenteral artesunate therapy, the fatality rate of cerebral malaria remains high. Adjunctive therapy targeting the underlying pathophysiology of cerebral malaria may further improve the clinical outcome. Endothelial activation and dysfunction is a central process in the pathogenesis of cerebr...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e328345a4cf
更新日期:2011-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Therapy-related myelodysplastic syndromes and acute myelogenous leukemia (t-MDS/AML) comprise an increasingly common, poor-risk disease cohort without standard treatment options. This review describes available treatments and recent advances that may influence the clinical management of t-MDS/AML. RE...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32835d82e6
更新日期:2013-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Obesity has become a worldwide epidemic that is driving increased morbidity and mortality from thrombotic disorders such as myocardial infarction, stroke, and venous thromboembolism. Effective prevention and treatment of thrombosis in obese patients is limited by an incomplete understanding of the und...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283634443
更新日期:2013-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Cellular to animal to human studies are shedding light on metabolic pathways that contribute to sustaining lymphomagenesis. Old players with new metabolic tricks and new metabolic players come into the scene. The purpose of this review is to discuss the recent advances made in the field of lymphoma me...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283623d16
更新日期:2013-07-01 00:00:00