Abstract:
:The search for, and discovery of, a physiologic model in which the developmentally regulated switch from fetal to adult globin gene expression could be prevented has resulted in the development of a new class of therapeutic agents, consisting of simple fatty acids, such as butyric acid, for the treatment of the beta-hemoglobinopathies. Butyrate and related drugs stimulate fetal (gamma-) globin gene expression in erythroid cells cultured from patients, and in chicken, ovine, and primate animal models. The butyrates are perhaps the first class of drugs designed to transcriptionally activate specific genes--in this particular case, to reactivate the developmentally silenced fetal globin genes. Phase I-II clinical trials resulting from this basic research have been initiated on a small scale during the past 3 years. Analysis of two butyrate-derived therapeutic agents, one delivered intravenously and one orally, has shown initial efficacy in stimulating fetal hemoglobin expression in 50% to 85% of patients. Correction of the anemia from the beta-hemoglobinopathy has followed induction of fetal globin, and has been adequate to eliminate the need for erythrocyte transfusions in some patients with beta-thalassemia. These compounds have been relatively safe and without generalized cytotoxicity in patients, but drug tolerance develops in some patients after prolonged therapy. Third-generation, small two- to five-carbon butyrate derivatives are in development. The molecular basis for butyrate action is being defined. Binding of putative regulatory proteins to a specific region of the gamma-globin promoter is altered in vivo in patients receiving butyrate therapy. Further analysis of the mode of action may contribute to development of other therapeutic agents designed to regulate gene transcription.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Faller DV,Perrine SPdoi
10.1097/00062752-199502020-00002subject
Has Abstractpub_date
1995-03-01 00:00:00pages
109-17issue
2eissn
1065-6251issn
1531-7048journal_volume
2pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:The proteome is the pool of proteins expressed at a given time and circumstance. The word 'proteomics' summarizes several technologies for visualization, quantitation and identification of these proteins. Recent advances in these techniques are helping to elucidate platelet processes which are relevan...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832e9dc6
更新日期:2009-09-01 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
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journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199603010-00007
更新日期:1996-01-01 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:PURPOSE OF REVIEW:This review summarizes recent advances in the application of minimal residual disease (MRD) testing in childhood acute lymphoblastic leukemia (ALL). RECENT FINDINGS:Polymerase chain reaction amplification of antigen receptor genes, one of the two main methods to study MRD in ALL, could be made more r...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283543d5c
更新日期:2012-07-01 00:00:00
abstract:PURPOSE OF REVIEW:Microtransplantation (or micro-stem cell transplantation, MST) is one permutation of alloreactive immunotherapy increasingly studied in clinical trials. It is most commonly applied to patients with myeloid malignancies who are not suitable candidates for allogeneic hematopoietic cell transplantation. ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000539
更新日期:2019-11-01 00:00:00
abstract:PURPOSE OF REVIEW:Graft-versus-host disease is one of the commonest complications of allogeneic bone marrow or peripheral blood stem cell transplantation. This review will cover advances in the pathophysiology of graft-versus-host disease and new agents under investigation for the treatment of this disorder. Patients d...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000148763.12733.bb
更新日期:2005-01-01 00:00:00
abstract:PURPOSE OF REVIEW:To review the data on angiogenesis related to exosomes secreted by tumor cells in hematologic neoplasia and to elucidate the role of exosomes and exosomal miRNA in the bone marrow microenvironment, especially under hypoxic conditions. RECENT FINDINGS:Cross-talk between bone marrow tumor cells and sur...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000235
更新日期:2016-05-01 00:00:00
abstract::The advent of better diagnostic tools, molecular techniques, and cytokine therapies have come together at the end of the 20th century to provide an improved outlook for patients with autoimmune neutropenia. Severe chronic neutropenia is no longer idiopathic in most cases, and growth factor therapy can be safely offere...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200105000-00007
更新日期:2001-05-01 00:00:00
abstract::Matching for human leukocyte antigen (HLA) loci is the most crucial factor in the selection of bone marrow donors. The techniques utilized to assign HLA type have evolved significantly since the application of polymerase chain reaction-based methodologies. A significant challenge for DNA typing methodologies is to be ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199811000-00012
更新日期:1998-11-01 00:00:00
abstract::This article presents the most recent insights into the biology, prognostic significance, and therapeutic approaches to TEL/AML1-positive leukemia. The TEL/AML1 fusion gene, also known as ETV6 /CBFA2, is the most commonly occurring gene rearrangement in pediatric acute lymphoblastic leukemia (ALL). Considerable contro...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200207000-00013
更新日期:2002-07-01 00:00:00
abstract:PURPOSE OF REVIEW:Hematopoietic cell transplantation offers potentially curative therapy for patients with myelodysplastic syndrome. The median patient age at diagnosis, however, is about 70 years, which has limited the application of conventional hematopoietic cell transplantation. In addition, the optimum timing of t...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000208466.63861.9f
更新日期:2006-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Despite improvements in the achievement of complete remission and progress in the supportive care of adults with acute lymphoblastic leukemia during the last decade, the majority of patients have eventually relapsed with overall survival in adult acute lymphoblastic leukemia of only 30-40%. However, t...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283034697
更新日期:2008-07-01 00:00:00
abstract::Commitment of hematopoietic cells to the erythroid lineage involves the actions of several transcription factors, including TAL1, LMO2, and GATA-2. The differentiation of committed erythroid progenitor cells involves other transcription factors, including NF-E2 and EKLF. Upon binding erythropoietin, the principal regu...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200203000-00002
更新日期:2002-03-01 00:00:00
abstract:PURPOSE OF REVIEW:To highlight mechanisms that regulate the balance between latent and active von Willebrand factor (VWF), and describe pathological conditions leading to increased levels of active VWF. RECENT FINDINGS:Levels of circulating active VWF are increased in von Willebrand disease type 2B, HELLP syndrome, ma...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3280dce531
更新日期:2007-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), despite improvements in our understanding of its pathophysiology as well as the generation of new monoclonal antibodies, immunomodulatory chemotherapy, cellular ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283319a6f
更新日期:2009-11-01 00:00:00
abstract::Anemia is a common disorder in patients with cancer and can be caused by the disease itself or by cancer-related therapy. The cardinal symptom of anemia, fatigue, is the most commonly reported symptom in patients with cancer and has profound effects on patient well-being and quality of life. Until recently, blood tran...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200205000-00010
更新日期:2002-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Clonal heterogeneity is a significant obstacle to successful treatment of patients with acute myeloid leukemia (AML). Here, we review new advances in the understanding of genetic heterogeneity in AML using single-cell DNA-sequencing technology. RECENT FINDINGS:New genomics and immunologic discovery t...
journal_title:Current opinion in hematology
pub_type: 杂志文章
doi:10.1097/MOH.0000000000000626
更新日期:2021-01-01 00:00:00
abstract::Advances in platelet transfusion have contributed to improved outcomes in the treatment of patients with cancer and leukemia. However, the optimal strategies to avoid some of the side effects that could result from platelet transfusions remain under investigation. These side effects include the development of refracto...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199603050-00003
更新日期:1996-09-01 00:00:00
abstract:PURPOSE OF REVIEW:The leukocyte adhesion deficiency (LAD) syndromes are rare genetically determined conditions with challenging clinical features. These immunodeficiencies also provide insights that are broadly relevant to the biology of leukocytes, platelets, intercellular interactions, and intracellular signaling. Re...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32835a0091
更新日期:2013-01-01 00:00:00
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journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32830a9746
更新日期:2008-09-01 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: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::The risk of transmission of viruses and other pathogenic organisms by blood can be reduced but not eliminated through donor selection and screening methodologies. The safety of blood derivatives prepared from plasma pools from thousands of donors requires virus inactivation, without which transmission rates approach c...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502060-00014
更新日期:1995-11-01 00:00:00
abstract::Several methods to model human Ph+ leukemia in laboratory mice are available, including propagation of BCR/ABL-expressing cells in mice, xenotransplantation of primary Ph+ leukemia cells into immunodeficient mice, BCR/ABL transgenic mice, and BCR/ABL retroviral bone marrow transduction and transplantation. Recent stud...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200107000-00008
更新日期:2001-07-01 00:00:00
abstract::Leukocytes use an array of antimicrobial peptides and proteins to help them destroy invading microorganisms. These endogenous antibiotic molecules are remarkable for their structural variety, rapid evolutionary divergence, intraspecies variation, and complex yet subtle interactions with their targets. This arsenal has...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704010-00009
更新日期:1997-01-01 00:00:00
abstract::The bulk of antigens that are presented by major histocompatibility complex (MHC) class I molecules are processed in the cytosol. Therefore, the cellular protein degradation machinery is thought to play a major role in antigen processing. For example, there is clear evidence that the ubiquitin-proteasome pathway, the ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200101000-00003
更新日期:2001-01-01 00:00:00
abstract::Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder comprising approximately 2 to 3% of all adult leukemias in the United States. Hairy cells are clonal expansions of mature, activated B-cells. They co-express CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal immunoglobul...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200307000-00002
更新日期:2003-07-01 00:00:00
abstract::Multiple myeloma is the second most common hematologic malignancy, with approximately 15,000 new cases each year in the United States. Our understanding of the pathophysiology underlying myeloma continues to expand, but the cause of this plasma cell dyscrasia remains unclear. Though controversy remains regarding a pos...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200007000-00007
更新日期:2000-07-01 00:00:00
abstract::D-dimer, a breakdown product of cross-linked fibrin has been extensively evaluated as a diagnostic test for acute venous thromboembolism. Rapid, highly sensitive D-dimer assays are now available that are suitable for testing in the emergency setting. Preliminary studies suggest that when using a highly sensitive D-dim...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200009000-00007
更新日期:2000-09-01 00:00:00