Abstract:
:Mechanisms of resistance to the tyrosine kinase inhibitor (TKI) imatinib had been modeled in vitro even prior to the first reports of clinical resistance in patients with chronic myeloid leukemia (CML). The discovery that BCR-ABL is reactivated at the time of resistance and the unveiling of point mutations within the kinase domain of BCR-ABL as a major resistance mechanism have driven the development of second-generation TKIs. These agents are effective in a significant proportion of patients who fail to respond to imatinib. Clinical practice guidelines recommend using the BCR-ABL mutation genotype to aid selection of second-line treatment. Although kinase domain mutations are undoubtedly relevant to drug resistance, recent data suggest that additional resistance mechanisms must be operational in patients with and without kinase domain mutations. Clonal chromosomal evolution, BCR-ABL amplification, pharmacogenomic variations, or activation of signaling shortcuts have all been implicated in drug resistance, but their precise contributions to resistance remain to be determined. Additionally, lack of adherence to prescribed medication is likely to set the stage for resistance development. An area of intense research is primary resistance of leukemic stem cells (LSCs), which are thought to cause minimal residual disease to persist despite sustained treatment. The intent of this review is to shed light on the various aspects of TKI resistance in CML with respect to their biology and clinical implications.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
La Rosée P,Deininger MWdoi
10.1053/j.seminhematol.2010.06.005subject
Has Abstractpub_date
2010-10-01 00:00:00pages
335-43issue
4eissn
0037-1963issn
1532-8686pii
S0037-1963(10)00079-Xjournal_volume
47pub_type
杂志文章,评审abstract::Since warfarin remains the predominate drug administered for long-term anticoagulation, optimizing therapy for maximum antithrombotic effect with minimal bleeding risk continues to challenge clinicians. Genetic differences exist that affect an individual's response to warfarin. The clinician can use genetic informatio...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/shem.2002.34089
更新日期:2002-07-01 00:00:00
abstract::Gene expression profiling of cancer began as a research tool but is rapidly moving towards clinical application. The diagnostic category of diffuse large B-cell lymphoma (DLBCL) can now be viewed as an amalgam of several different diseases that have distinct gene expression profiles, oncogenic mechanisms, and clinical...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(03)00194-x
更新日期:2003-10-01 00:00:00
abstract::The successful clinical development of thalidomide, bortezomib, and lenalidomide not only transformed the therapeutic management of multiple myeloma (MM) but also catalyzed a renewed interest in the development of additional classes of novel agents for this disease. This review focuses on a series of new therapeutics ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2009.02.003
更新日期:2009-04-01 00:00:00
abstract::Purine analogues have been shown to be active in a variety of B- and T-cell malignancies. Among them, pentostatin is also a tight binding inhibitor of adenosine deaminase (ADA), a key enzyme of purine metabolism. ADA is present in all human tissues, with the highest levels in the lymphoid system. Early clinical trials...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2005.12.005
更新日期:2006-04-01 00:00:00
abstract::Mechanisms that support migration of leukocytes have been studied extensively in vitro. The adhesion of neutrophils under conditions of flow at venous shear rates primarily involves members of the selectin family. E-selectin is upregulated by cytokine stimulation of endothelial cells (ECs); P-selectin is upregulated b...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::A retrospective study was conducted to determine treatment patterns for idiopathic thrombocytopenia purpura (ITP) across the US and to determine the cost of its treatment with high-dose intravenous immunoglobulin (IVIg) and anti-D therapy. Information on the incidence, treatment patterns, hospital care, and costs for ...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Shwachman-Diamond syndrome (SDS) is an autosomal recessive marrow failure syndrome associated with exocrine pancreatic insufficiency and leukemia predisposition. Bone marrow failure typically manifests with neutropenia, but anemia, thrombocytopenia, or aplastic anemia may also develop. Additional organ systems, such a...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2006.04.006
更新日期:2006-07-01 00:00:00
abstract::There are now more than 25 million volunteer donors registered worldwide for patients in need of a life-saving hematopoietic cell transplant to cure blood disorders. Although a human leukocyte antigen (HLA)-matched donor remains the preferred stem cell source for transplantation, the use of a donor with limited HLA mi...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2016.07.003
更新日期:2016-10-01 00:00:00
abstract::Antibody-mediated rejection (AMR) is a major risk factor for graft loss following kidney transplantation. Traditional anti-humoral therapies provide suboptimal therapy and they do not deplete plasma cells, which are the source of antibody production. Proteasome inhibitors (PI) have been shown to deplete both transform...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2012.04.008
更新日期:2012-07-01 00:00:00
abstract::Copper is an essential trace element that is required for a number of enzymes which are necessary for normal metabolic function. Metabolic balance studies have demonstrated that daily copper losses are approximately 1.3 mg/day. In order to remain in copper balance, the average adult male must consume a diet which cont...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1983-04-01 00:00:00
abstract::Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administr...
journal_title:Seminars in hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::Thrombosis is a common and potentially serious complication of immune-mediated heparin-induced thrombocytopenia (HIT). Discontinuation of heparin is a simple and important maneuver in patients with suspected HIT. Unfortunately, thrombosis often occurs even in those patients in whom heparin was discontinued because of ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 00:00:00
abstract::The use of combination chemotherapy has been successful in treating advanced or widespread Hodgkin's disease (HD). For patients with relapsed disease, the long-term prognosis is much poorer, despite the good rate of reinduction into a second or further remission using conventional treatments. The majority of such pati...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-07-01 00:00:00
abstract::Even though the overall outcome after allogeneic transplant has improved significantly in the last decades, late infectious diseases are still the most important causes of late morbidity and mortality. Here, impaired immune reconstitution and therapy of chronic graft-versus-host disease (GVHD) represent the major risk...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2011.10.009
更新日期:2012-01-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenia and by increased progression to acute myelocytic leukemia (AML). With the exception of allogeneic stem cell transplantation, there is generally no curative treatment for these d...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2004.02.002
更新日期:2004-04-01 00:00:00
abstract::Stem cell transplantation is a recognized treatment for many hematologic malignancies. Human leukocyte antigen (HLA) testing is a key assessment in the evaluation of potential recipients and selection of the appropriate stem cell donor. Over the past several years, technological advances have moved HLA testing from a ...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(01)90052-6
更新日期:2001-04-01 00:00:00
abstract::Thrombopoietin (TPO) regulates thrombopoiesis through activation of TPO receptors on the megakaryocyte cell surface, resulting in increased platelet production. The TPO receptor agonists are novel treatments for patients with chronic ITP aimed at increasing platelet production through interactions with the TPO recepto...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2013.03.005
更新日期:2013-01-01 00:00:00
abstract::For the majority of hematologic malignancies allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option. Sibling donors have been the standard for adult patients. Since there is not a suitable family donor for all patients, the need for alternative donors for HCT is great. Fortunately, t...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2016.01.009
更新日期:2016-04-01 00:00:00
abstract::Anemia is frequent and significantly adds to the morbidity of cancer patients, and has been associated with decreased quality of life (QOL). Three open-label community-based studies of epoetin alfa in cancer-related anemia (two using three-times-weekly dosing and one using once-weekly dosing) in more than 7,000 patien...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90062-3
更新日期:2000-10-01 00:00:00
abstract::Traditionally, acute myeloid leukemia (AML) has been diagnosed and classified based on the morphologic and cytochemical criteria of the French-American-British (FAB) classification system. However, more recent studies have demonstrated that the cytogenetic and molecular genetic abnormalities consistently associated wi...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::The introduction of chimeric antigen receptor (CAR) T-cell therapy in acute lymphoblastic leukemia (ALL) has dramatically altered the landscape of treatment options available to children and adults with ALL. With complete remission induction rates exceeding 70% in most trials and FDA approval of one CD19 CAR T-cell co...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2020.07.002
更新日期:2020-07-01 00:00:00
abstract::In early studies, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been found to reduce the depth and duration of granulocytopenia in the settings of cancer chemotherapy and autologous bone marrow transplantation. In patients with myelodysplastic syndrome or aplastic anemia. GM-CSF has p...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1990-07-01 00:00:00
abstract::In the era of modern communication, the physician and patient relationship has evolved to include an entirely new dimension-social media. This new dimension offers several opportunities for patient education, research and its dissemination, and professional development for health care providers; it can also serve as a...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2017.07.003
更新日期:2017-10-01 00:00:00
abstract::TET2 is one of the most frequently mutated genes in myeloid neoplasms. TET2 loss-of-function perturbs myeloid differentiation and causes clonal expansion. Despite extensive knowledge regarding biochemical mechanisms underlying distorted myeloid differentiation, targeted therapies are lagging. Here we review known bioc...
journal_title:Seminars in hematology
pub_type: 杂志文章
doi:10.1053/j.seminhematol.2020.12.002
更新日期:2021-01-01 00:00:00
abstract::Mantle cell lymphoma (MCL) has only recently been recognized as a separate biologically defined lymphoma entity. Due to its low incidence, many reports on clinical prognostic factors are limited by small patient numbers. The MCL International Prognostic Index (MIPI) was developed using data of more than 400 patients t...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2011.06.001
更新日期:2011-07-01 00:00:00
abstract::These two issues of the Seminars in Hematology will provide the physician the necessary knowledge to help make sense of this somewhat confusing array of diseases. The subdivisions of MDS reflect the precision of our techniques of dissection, with morphological and histochemical analyses forming the foundation to ident...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1996-04-01 00:00:00
abstract::Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched sibling is the treatment of choice in children and young adults with severe aplastic anemia (SAA). However, because only 30% of patients have a suitable donor, more aggressive nontransplant immunosuppressive regimens have been used, with re...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90029-5
更新日期:2000-01-01 00:00:00
abstract::Familial thrombosis has long been considered as an autosomal dominant trait, caused by a dominant gene defect with a reduced penetrance for the disease. Recently, this view has changed and today familial thrombophilia is considered as a complex genetic disorder caused by the segregation of two or more gene defects (kn...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 00:00:00
abstract::The virome has been recently studied in hematology and mostly in the setting of allogeneic hematopoietic stem cell transplantation. However, in hematology (as in the setting of nonhematological disorders) the study of the microbiome (that indeed includes the virome) is a growing field. The overall field is moving beyo...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1053/j.seminhematol.2020.05.001
更新日期:2020-01-01 00:00:00
abstract::Idiopathic thrombocytopenic purpura (ITP) is an illness of primary acquired thrombocytopenia occurring in the absence of marrow failure. Splenectomy was first used as a treatment for ITP in 1913. However, with the realization that opsonin (critical for the optimal killing of invasive micro-organisms by white blood cel...
journal_title:Seminars in hematology
pub_type: 杂志文章,评审
doi:10.1016/s0037-1963(00)90114-8
更新日期:2000-01-01 00:00:00