Abstract:
:Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by abnormal circulation and proliferation of malignant progenitors. In contrast to their normal counterparts, CML progenitors adhere poorly to bone marrow stroma or fibronectin (FN). Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal progenitors is also associated with inhibition of their proliferation. As the beta1 integrin expression on CML progenitors is normal, we hypothesized that decreased integrin affinity may underlie the abnormal adhesive and proliferative characteristics of CML progenitors. We examined the effect of affinity modulation by the activating antibody 8A2 on the adhesion and proliferation of CML progenitors and the CML cell line, K562. 8A2 induced alpha5Beta1-dependent adhesion of Philadelphia chromosome-positive (Ph+) CD34+/HLA-DR+ cells and K562 cells to FN. Increased adhesion was 8A2- and FN concentration-dependent, time-dependent, and energy-dependent. Further, 8A2-induced adhesion to FN significantly inhibited the proliferation of malignant CML progenitors as well as K562 cells independent of cell differentiation, necrosis, or apoptosis. These studies demonstrate that affinity modulation of the alpha5Beta1 integrin on CML progenitors and K562 cells by 8A2 results in increased adhesion to FN with subsequent decreased proliferation, suggesting that decreased beta1 integrin affinity contributes to the abnormal circulation and proliferation of malignant progenitors in CML.
journal_name
Bloodjournal_title
Bloodauthors
Lundell BI,McCarthy JB,Kovach NL,Verfaillie CMsubject
Has Abstractpub_date
1996-03-15 00:00:00pages
2450-8issue
6eissn
0006-4971issn
1528-0020journal_volume
87pub_type
杂志文章相关文献
BLOOD文献大全abstract::Natural killer (NK) cells play critical roles in protection against hematological malignancies but can acquire a dysfunctional state, which limits antitumor immunity. However, the underlying reasons for this impaired NK cell function remain to be uncovered. We found that NK cells in aggressive B-cell lymphoma underwen...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005602
更新日期:2020-12-24 00:00:00
abstract::Allogeneic stem cell transplantation (SCT) is a unique procedure, primarily in patients with hematopoietic malignancies, involving chemoradiotherapy followed by the introduction of donor hematopoietic and immune cells into an inflamed and lymphopenic environment. Interruption of the process by which recipient alloanti...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-02-697250
更新日期:2016-06-16 00:00:00
abstract::Genetic variation in the PEAR1 locus is linked to platelet reactivity and cardiovascular disease. The major G allele of rs12041331, an intronic cytosine guanine dinucleotide-single-nucleotide polymorphism (CpG-SNP), is associated with higher PEAR1 expression in platelets and endothelial cells than the minor A allele. ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-11-682153
更新日期:2016-08-18 00:00:00
abstract::Mutations of the NPM1 gene (NPM1mut) are among the most common genetic alterations in acute myeloid leukemia and are suitable for minimal residual disease detection. We retrospectively investigated the prognostic impact of NPM1mut-based minimal residual disease detection from bone marrow for development of relapse by ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-10-461749
更新日期:2013-07-04 00:00:00
abstract::We have identified and cloned a novel human cytokine with homology to cytokines of the interleukin-17 (IL-17) family, which we have termed human IL-17E (hIL-17E). With the identification of several IL-17 family members, it is critical to understand the in vivo function of these molecules. We have generated transgenic ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0012
更新日期:2002-10-01 00:00:00
abstract::The t(1;19)(q23;p13) chromosomal translocation is observed cytogenetically in 25% of children with pre-B-cell acute lymphoblastic leukemia (ALL) and is associated with an adverse treatment outcome. The t(1;19) juxtaposes the E2A gene from chromosome 19 with the PBX1 gene on chromosome 1, leading to the production of f...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-02-15 00:00:00
abstract::It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::Multiple myeloma (MM) is associated with severe normochromic/normocytic anemia. This study demonstrates that the abnormal up-regulation of apoptogenic receptors, including both Fas ligand (L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), by highly malignant myeloma cells is involved in the patho...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.4.1305
更新日期:2002-02-15 00:00:00
abstract::In order to determine if mutant hemoglobins can be identified by relatively simple methods, a Working Group of the ICSH Expert Panel on Abnormal Hemoglobins and Thalassemia analyzed 17 hemolysates containing 14 different mutant hemoglobins by four electrophoretic methods: (1) cellulose acetate in alkaline buffers, (2)...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1978-11-01 00:00:00
abstract::The administration of greater than or equal to 5 micrograms interleukin-7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Concurrent activation of the T-cell receptor (TCR) and complement regulator CD46 on human CD4+ T lymphocytes induces Tr1-like regulatory T cells that suppress through IL-10 secretion bystander T-cell proliferation. Here we show that, despite their IL-10 production, CD46-induced T-regulatory T cells (Tregs) do not supp...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-07-2951
更新日期:2006-02-15 00:00:00
abstract::Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications me...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-05-1986
更新日期:2004-12-15 00:00:00
abstract::One hundred seventy-nine patients with acute nonlymphoblastic leukemia in first remission (n = 75), chronic myelocytic leukemia in chronic or accelerated phase (n = 48) or leukemia in advanced stage (n = 56) were given HLA-identical marrow grafts and randomized to receive methotrexate or cyclosporine for prevention of...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1988-02-01 00:00:00
abstract::The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing periphe...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1975-07-01 00:00:00
abstract::Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-02-15 00:00:00
abstract::Initial molecular events leading to natural killer lymphocyte (NK) and dendritic cell (DC) interactions are largely unknown. Here, the role of CX3CL1 (fractalkine), a chemokine expressed on mature dendritic cells (mDCs) has been investigated. We show that CX3CL1 promotes NK activation by mDCs. After blocking of CX3CL1...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-12-126888
更新日期:2008-12-01 00:00:00
abstract::Mutations in the SH2D1A gene have been described in most patients with the clinical syndrome of X-linked lymphoproliferative disease (XLP). The diagnosis of XLP is still difficult given its clinical heterogeneity and the lack of a readily available rapid diagnostic laboratory test, particularly in patients without a f...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2004-09-3651
更新日期:2005-04-15 00:00:00
abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages to act as an erythroid burst-promoting activity and to stimulate limited replication of spleen colony-forming cells. Here we demonstrate that murine GM-CSF alone or in co...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha2b (3 MIU, 5 days/wk) or hydroxyurea...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1998-04-15 00:00:00
abstract::T-cell production depends on the recruitment of hematopoietic progenitors into the thymus. T cells are among the last of the hematopoietic lineages to recover after bone marrow transplantation (BMT), but the reasons for this delay are not well understood. Under normal physiologic conditions, thymic settling is selecti...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-324954
更新日期:2011-08-18 00:00:00
abstract::Fanconi anemia (FA) is an autosomal recessive syndrome characterized by progressive bone marrow failure and cancer predisposition. Eight FA complementation groups have been identified. The FANCA, FANCC, FANCE, FANCF, and FANCG proteins form a nuclear complex required for the monoubiquination of the FANCD2 protein. To ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-11-3517
更新日期:2003-07-01 00:00:00
abstract::Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene transcription are well understood, very little is known on the signaling events regulating RA-dependent initiation of mRNA translation. We examined whether the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-06-2078
更新日期:2005-02-15 00:00:00
abstract::Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor T cells ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-07-034157
更新日期:2007-05-01 00:00:00
abstract::Internal tandem duplication of the Fms-like tyrosine kinase-3 receptor (FLT3) internal tandem duplication (ITD) is found in 30% of acute myeloid leukemia (AML) and is associated with a poor outcome. In addition to tyrosine kinase inhibitors, therapeutic strategies that modulate the expression of FLT3-ITD are also prom...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-05-646497
更新日期:2016-02-18 00:00:00
abstract::Mutations of the type III receptor tyrosine kinase FLT3 occur in approximately 30% of acute myeloid leukemia patients and lead to constitutive activation. This has made FLT3-activating mutations an attractive drug target because they are probable driver mutations of this disease. As more potent FLT3 inhibitors are dev...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-10-529313
更新日期:2014-01-02 00:00:00
abstract::Acquired chromosomal anomalies (most commonly translocations) in lymphoma and leukemia usually result in either activation of a quiescent gene (by means of immunoglobulin or T-cell-receptor promotors) and expression of an intact protein product, or creation of a fusion gene encoding a chimeric protein. This review sum...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood.v99.2.409
更新日期:2002-01-15 00:00:00
abstract::The relative requirements of colonies derived from erythroid (BFU-E) and myeloid (CFU-c) progenitors for transferrin were examined using monoclonal antibodies directed against the transferrin molecule (TF-6) or its cell surface receptor (TFR-A12, TFR1-2B). Growth of erythroid bursts was profoundly reduced at concentra...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::CD8alpha+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8alpha+ DCs remains to be identified. We reported here that murine splenic CD8alpha+CD11c- lineage phenotype (Lin)- cel...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.2.569
更新日期:2002-07-15 00:00:00
abstract::Erythropoietin (EPO) and its receptor (EPOR) are required for the development of mature erythrocytes. After binding of ligand, the EPOR activates a variety of signaling pathways that ultimately control cellular proliferation, survival, and specific gene expression. Although erythroid progenitors appear to be the princ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have emerged as a promising tool for clinical application. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more important, display immunosuppressive capacities. These properties may be of therapeutic va...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-011650
更新日期:2006-09-15 00:00:00