Abstract:
:The acute myeloid leukemia (AML) treatment landscape has changed substantially since 2017. New targeted drugs have emerged, including venetoclax to target B-cell lymphoma 2, midostaurin and gilteritinib to target FLT3, and ivosidenib and enasidenib to target mutant isocitrate dehydrogenase 1 and 2, respectively. Other additions include reapproval of gemtuzumab ozogomycin to target CD33, glasdegib to target the hedgehog pathway, and a liposomal formulation of daunorubicin and cytarabine (CPX-351). Genomically heterogeneous AML has a tendency to evolve, particularly under selective treatment pressure. For decades, treatment decisions have largely centered around chemotherapy drug intensity. Physicians now have access to an increasing number of drugs with novel mechanisms of action and distinctive side-effect profiles. Key issues faced by hematologists in this era of new drugs include (1) the timely identification of actionable mutations at diagnosis and at relapse; (2) deciding which drug to use among several therapeutic options; and (3) increasing awareness of how to anticipate, mitigate, and manage common complications associated with these new agents. This article will use 3 case presentations to discuss some of the new treatment challenges encountered in AML management, with the goal of providing practical guidance to aid the practicing physician.
journal_name
Bloodjournal_title
Bloodauthors
DiNardo CD,Wei AHdoi
10.1182/blood.2019001239subject
Has Abstractpub_date
2020-01-09 00:00:00pages
85-96issue
2eissn
0006-4971issn
1528-0020pii
428884journal_volume
135pub_type
杂志文章相关文献
BLOOD文献大全abstract::We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published s...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Reconstitution of cytomegalovirus (CMV)-specific CD8(+) T cells is essential to the control of CMV infection in CMV-positive recipients (R(+)) after allogeneic hematopoietic stem cell transplantation (HCT). Six-color flow cytometry was used to assess the functional profile of CMV-specific CD8(+) T cells in 62 of 178 R...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-203307
更新日期:2009-06-18 00:00:00
abstract::Mice deficient in c-fms-like tyrosine kinase 3 (FLT3) signaling have reductions in early multipotent and lymphoid progenitors, whereas no evident myeloid phenotype has been reported. However, activating mutations of Flt3 are among the most common genetic events in acute myeloid leukemia and mice harboring internal tan...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-258756
更新日期:2010-06-17 00:00:00
abstract::Protein tyrosine phosphorylation plays a crucial role in signaling from the receptor for erythropoietin (Epo), although the Epo receptor (EpoR) lacks the tyrosine kinase domain. We have previously shown that the Jak2 tyrosine kinase couples with the EpoR to transduce a growth signal. In the present study, we demonstra...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::Best known for presenting antigenic peptides to CD4+ T cells, major histocompatibility complex class II (MHC II) also transmits or may modify intracellular signals. Here, we show that MHC II cell-autonomously regulates the balance between self-renewal and differentiation in B-cell precursors, as well as in malignant B...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-11-885467
更新日期:2019-03-07 00:00:00
abstract::Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-01-481713
更新日期:2013-08-15 00:00:00
abstract::Activation of inflammatory and procoagulant mechanisms is thought to contribute significantly to the initiation of restenosis, a common complication after balloon angioplasty of obstructed arteries. During this process, expression of tissue factor (TF) represents one of the major physiologic triggers of coagulation th...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-04-1148
更新日期:2004-03-01 00:00:00
abstract::Neutrophils play a crucial early role during the innate response, but little is known about their possible contribution when an adaptive immune response is installed. A robust neutrophilia and a T helper 1 (Th1) immune response are present after immunization with Complete Freund Adjuvant (CFA). We show that when FITC-...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-04-016659
更新日期:2006-11-01 00:00:00
abstract::Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outcome of patients wit...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2014-11-608075
更新日期:2015-03-26 00:00:00
abstract::Prothrombin activation can proceed through the intermediates meizothrombin or prethrombin-2. To assess the contributions that these 2 intermediates make to prothrombin activation in tissue factor (Tf)-activated blood, immunoassays were developed that measure the meizothrombin antithrombin (mTAT) and α-thrombin antithr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-05-427856
更新日期:2012-11-01 00:00:00
abstract::The MLLT10 gene, located at 10p13, is a known partner of MLL and PICALM in specific leukemic fusions generated from recurrent 11q23 and 11q14 chromosome translocations. Deep sequencing recently identified NAP1L1/12q21 as another MLLT10 partner in T-cell acute lymphoblastic leukemia (T-ALL). In pediatric T-ALL, we have...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-02-487256
更新日期:2013-06-20 00:00:00
abstract::During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming un...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-07-01 00:00:00
abstract::We developed 2bF9 transgenic mice in a hemophilia B mouse model with the expression of human factor IX (FIX) under control of the platelet-specific integrin alphaIIb promoter, to determine whether ectopically expressing FIX in megakaryocytes can enable the storage of FIX in platelet alpha-granules and corrects the mur...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-11-255612
更新日期:2010-08-26 00:00:00
abstract::Surprisingly little is known about the interaction of human blood mononuclear cells with viruses. Here, we show that monocytes are the predominant cell type infected when peripheral blood mononuclear cells are exposed to viruses ex vivo. Remarkably, infection with vesicular stomatitis virus, vaccinia virus, and a vari...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-379479
更新日期:2012-03-29 00:00:00
abstract::Identification of prognostic factors for patients with relapsed/refractory Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase 2 study of positron emission tomography (PET)-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-06-788877
更新日期:2017-11-16 00:00:00
abstract::The role of interleukin-12 (IL-12) in Th1 cell differentiation is well established. The heterodimer p70, composed of a p40 and a p35 chain, is the biologically active form. IL-12 production by human monocytes is enhanced by interferon-gamma (IFN-gamma) and inhibited by IL-10 and prostaglandin E2 (PGE2). Peripheral blo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-01-15 00:00:00
abstract::The molecular backgrounds of variants encountered in Afro-Caribbean black individuals and associated with the production of clinically significant antibodies against high-incidence antigens (anti-RH18, anti-RH34) and against Rhe epitopes were determined. We showed that RH:-18 phenotypes are produced by 3 distinct RHCE...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0229
更新日期:2002-12-01 00:00:00
abstract::Natural-killer (NK)-cell dysfunction and IFN-gamma deficiencies have been associated with increased incidence of both malignancy and infection. The immunologic basis of NK-cell defects in cancer-bearing hosts has not been extensively studied. Here, we demonstrate that multiple lineages of tumors, including thymoma, br...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-4535
更新日期:2006-07-01 00:00:00
abstract::Human recombinant interleukin-4 (IL-4) was studied for its effects on myeloid progenitor cells from normal and leukemic bone marrow cells in the presence and absence of additional growth factors. IL-4 itself did not support myeloid cluster or colony formation (CFU-GM). However, cultures supplied with IL-4 (300 U/mL) a...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Immune thrombocytopenias are usually associated with normal or increased numbers of megakaryocytes in the marrow. Therefore, the mechanism(s) responsible for the destruction of circulating platelets may not affect megakaryocytes in the same way. One of the possibilities which could account for the differential effect ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::Sixteen patients treated by allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr/abl-specific RNA transcripts at various time points after BMT. In reconstitution experiments, one CML cell per million normal mononuclear cells c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::The developmental relationship between the blood and endothelial cell (EC) lineages remains unclear. In the extra-embryonic blood islands of birds and mammals, ECs and blood cells are closely intermixed, and blood island precursor cells in the primitive streak express many of the same molecular markers, leading to the...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-03-490045
更新日期:2013-12-05 00:00:00
abstract::It has been suggested that human cytomegalovirus (HCMV) evades the immune system by infecting and paralyzing antigen-presenting cells. This view is based mainly on studies of dendritic cells (DCs) obtained after culture of monocytes (moDCs). It is contradicted by the asymptomatic course of HCMV infection in healthy pe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-05-2016
更新日期:2006-03-01 00:00:00
abstract::We have been transducing mouse hematopoietic cells with the human MDR1 (MDR) gene in retroviral vectors to determine the optimal conditions for retroviral gene transfer as a model system for potential human gene therapy. In these studies, we have demonstrated transduction and expression of the human MDR gene using eco...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-07-15 00:00:00
abstract::We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increas...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-11-15 00:00:00
abstract::Bax is a proapoptotic member of the Bcl-2 protein family. The incidence and prognostic significance of Bax protein expression in diffuse non-Hodgkin's lymphomas with a large cell component (DLCL) was determined by an immunohistochemical method by using paraffin-embedded tumors from a cohort of patients treated uniform...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-10-15 00:00:00
abstract::Hepcidin is the principal iron regulatory hormone and its overproduction contributes to anemia of inflammation (AI). In vitro, hepcidin binds to and induces the degradation of the exclusive iron exporter ferroportin. We explored the effects and distribution of synthetic hepcidin in the mouse. A single intraperitoneal ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-04-1766
更新日期:2005-09-15 00:00:00
abstract::Human band 3 Walton is an AE1 mutation that results in the deletion of the 11 COOH-terminal amino acids of the protein and is associated with dominant distal renal tubular acidosis. The properties of band 3 Walton expressed with normal band 3 in the heterozygous mutant erythrocytes and the kidney isoform expressed in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.1.342
更新日期:2002-01-01 00:00:00
abstract::The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia w...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-12-15 00:00:00