Abstract:
:CD44 is a widely expressed, multifunctional, cell-surface glycoprotein that has been implicated in the regulation of normal hematopoiesis. In addition, expression of particular isoforms of CD44 has been associated with malignant transformation and/or the acquisition of metastatic potential. In this study, we used two recently developed monoclonal anti-CD44 antibodies, one reactive with an epitope shared by many CD44 isoforms and the other with an epitope unique to CD44 isoforms containing amino acids encoded by the alternatively spliced exon v10, to compare the expression of CD44 on primitive hematopoietic cells from the marrow of normal individuals and their neoplastic counterparts present in the peripheral blood of patients with chronic myeloid leukemia (CML). Multiparameter fluorescence-activated cell sorter (FACS) analysis and cell sorting studies showed that CD44 is normally expressed at high to very high levels on both long-term culture-initiating cells (LTC-IC) and granulopoietic colony-forming cells (granulocyte-macrophage colony-forming units [CFU-GM]). In contrast, primitive erythropoietic progenitors (burst-forming units-erythroid [BFU-E]) in normal marrow were more homogeneous in their expression of CD44, and very few (less than 5%) showed the very high levels of CD44 seen on 20% to 25% of LTC-IC and CFU-GM. Antibody staining showed the expression of exon v10-containing CD44 isoforms to be restricted to a small subpopulation (4% to 8%) of morphologically recognizable mature (CD34-) myeloid cells within the light-density fraction of normal marrow cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed the presence of two exon v10-containing mRNA species. In CML, a significantly greater proportion of the circulating neoplastic CFU-GM expressed very high levels of CD44, and these CFU-GM were accompanied by an increased number of light density v10+ cells, including some that coexpressed CD34. Nonmalignant hematopoietic progenitors mobilized by prior chemotherapy and growth factor treatment of patients with Hodgkin's disease or acute myeloid leukemia in remission showed no changes in CD44 expression relative to normal marrow progenitors. These results provide evidence of early differentiation-associated changes in CD44 expression during normal hematopoiesis in vivo that may be deregulated in the neoplastic clone of patients with CML.
journal_name
Bloodjournal_title
Bloodauthors
Ghaffari S,Dougherty GJ,Lansdorp PM,Eaves AC,Eaves CJsubject
Has Abstractpub_date
1995-10-15 00:00:00pages
2976-85issue
8eissn
0006-4971issn
1528-0020journal_volume
86pub_type
杂志文章相关文献
BLOOD文献大全abstract::Measurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2* ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-10-3982
更新日期:2005-08-15 00:00:00
abstract::Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplant reflects a complex immune response resulting in chronic damage to multiple tissues. Previous studies indicated that donor B cells and the antibodies they produce play an important role in the development of cGVHD. To understa...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-08-801001
更新日期:2017-12-28 00:00:00
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...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019001239
更新日期:2020-01-09 00:00:00
abstract::Antisense oligodeoxynucleotide (ODN) drugs might be more effective if their delivery was optimized and they were targeted to short-lived proteins encoded by messenger RNA (mRNA) species with equally short half-lives. To test this hypothesis, an ODN targeted to the c-myb proto-oncogene was developed and used to purge m...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood.v99.4.1150
更新日期:2002-02-15 00:00:00
abstract::Stem cell localization, conservation, and differentiation is believed to occur in niches in the marrow stromal microenvironment. Our recent observation that long-term in vitro human hematopoiesis requires a stromal heparan sulfate proteoglycan (HSPG) led us to hypothesize that such HSPG may orchestrate the formation o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-15 00:00:00
abstract::Fibrin is essential for hemostasis; however, abnormal fibrin formation is hypothesized to increase thrombotic risk. We previously showed that in situ thrombin generation on a cell's surface modulates the 3-dimensional structure and stability of the fibrin network. Currently, we compared the abilities of extravascular ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-06-228940
更新日期:2009-11-26 00:00:00
abstract::Light-mediated release of signaling ligands, such as chemoattractants, growth factors, and cytokines is an attractive strategy for investigation and therapeutic targeting of leukocyte communication and immune responses. We introduce a versatile optogenetic method to control ligand secretion, combining UV-conditioned e...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-11-684852
更新日期:2016-06-09 00:00:00
abstract::The successful induction of a T-cell-mediated tumor-protective immunity against poorly immunogenic malignancies remains a major challenge for cancer immunotherapy. We achieved this by immunization with a tyrosine hydroxylase (mTH)-based DNA vaccine, enhanced with the posttranscriptional regulatory acting RNA element (...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-02-0391
更新日期:2003-01-15 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and muri...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-06-15 00:00:00
abstract::To address the mechanism by which the human globin genes are activated during erythropoiesis, we have used a tiled microarray to analyze the pattern of transcription factor binding and associated histone modifications across the telomeric region of human chromosome 16 in primary erythroid and nonerythroid cells. This ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-06-097964
更新日期:2007-12-15 00:00:00
abstract::Peripheral blood progenitor cells (PBPCs) are increasingly being used to replace bone marrow cells (BMCs) as a source of hematopoietic stem cells also in the field of allogeneic transplantation. Whereas it is well known that PBPC grafts and BM differ significantly in progenitor cell content and lymphocyte dose, the cl...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-08-15 00:00:00
abstract::Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mu...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-03-147090
更新日期:2008-09-01 00:00:00
abstract::Deletion of TP53 gene, under routine assessment by fluorescence in situ hybridization analysis, connects with the worst prognosis in chronic lymphocytic leukemia (CLL). The presence of isolated TP53 mutation (without deletion) is associated with reduced survival in CLL patients. It is unclear how these abnormalities a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-07-234708
更新日期:2009-12-17 00:00:00
abstract::A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated ad...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::Adherent cell layers and their associated extracellular matrices form when human marrow is incubated in cultures containing hydrocortisone and horse serum. These stromal layers contain cells positive for alkaline phosphatase; secrete collagens types I and III and fibronectin, bind the anti-actin monoclonal antibodies ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-05-15 00:00:00
abstract::In this issue of Blood, Baychelier et al identify a ligand for a major natural killer (NK) cell receptor that mediates natural cytotoxicity toward tumor cells, thus ending a search that lasted well over a decade. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2013-09-523696
更新日期:2013-10-24 00:00:00
abstract::Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A cha...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is an immune deficiency linked in many cases to heterozygous mutations causing truncations in the cytoplasmic tail of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXC...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-07-102103
更新日期:2008-07-01 00:00:00
abstract::Retention of lipoproteins within the vasculature is a central event in the pathogenesis of atherosclerosis. However, the signals that mediate this process are only partially understood. Prompted by putative links between inflammation and atherosclerosis, we previously reported that alpha-defensins released by neutroph...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-09-15 00:00:00
abstract::In addition to its importance in transfusion, Kell protein is a member of the M13 family of zinc endopeptidases and functions as an endothelin-3-converting enzyme. To obtain information on the structure of Kell protein we built a model based on the crystal structure of the ectodomain of neutral endopeptidase 24.11 (NE...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-05-1564
更新日期:2003-10-15 00:00:00
abstract::In human follicular lymphoma the t(14; 18) chromosome translocation activates the antiapoptotic oncogene Bcl2 by linking it to the immunoglobulin heavy chain (IGH) locus. Transgenic mice expressing Bcl2 controlled by an Igh enhancer (E mu) do not develop follicular lymphoma, although they do have an increased incidenc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-07-2469
更新日期:2004-03-15 00:00:00
abstract::Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1)...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-04-499558
更新日期:2013-11-07 00:00:00
abstract::The morphologic, immunophenotypic, genotypic, genomic, and functional features of an undifferentiated acute leukemia with stem cell features are reported. At light and electron microscopy, the leukemic population was represented by primitive progenitor cells with no evidence of differentiation. The blasts were CD34(+)...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.12.4634
更新日期:2002-06-15 00:00:00
abstract::Development of inhibitory antibodies is a serious complication of treatment with repeated factor IX infusions in a minority of patients with hemophilia B. Such antibodies detected in 8 patients have been characterized. Typing studies revealed that patients' immune response toward factor IX is highly heterogeneous and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.5.1416
更新日期:2001-09-01 00:00:00
abstract::Patients referred to tertiary care centers occasionally may have their diagnostic procedures repeated and have a final diagnosis that differs from that of the referring center. The aim of this study was to evaluate discordance rates and their clinical implications in the diagnosis of patients with myelodysplastic synd...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-342642
更新日期:2011-10-27 00:00:00
abstract::Although combination regimens have improved outcomes over monotherapy in chronic lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine, cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided synergistic cytotoxicity with effective clearing of minimal residual disease. Th...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2011-05-351833
更新日期:2011-10-13 00:00:00
abstract::Cumulative evidence indicates that MYC, one of the major downstream effectors of NOTCH1, is a critical component of T-cell acute lymphoblastic leukemia (T-ALL) oncogenesis and a potential candidate for targeted therapy. However, MYC is a complex oncogene, involving both fine protein dosage and cell-context dependency,...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-336842
更新日期:2011-06-16 00:00:00
abstract::The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-09-806844
更新日期:2018-03-22 00:00:00
abstract::Expression of the von Willebrand factor (vWF) gene is restricted to the endothelial and megakaryocyte lineages. Within the endothelium, expression of vWF varies between different vascular beds. We have previously shown that the human vWF promoter spanning a region between -2182 (relative to the start site of transcrip...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00