Abstract:
:The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tumor tissue but is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream. In total, >1400 proteins were identified. Overall, 181 proteins were >100-fold overexpressed in AML as compared with normal BM. Eleven of the most differentially expressed proteins were further validated by immunohistochemistry and confocal microscopic analyses, including novel antigens highly expressed in AML cells (for example, adaptor-related protein complex 3 β2) and in the leukemia-modified extracellular matrix (ECM) (for example, collagen-VI-α-1). The presented atlas of targetable AML-associated BM proteins provides a valuable basis for the development of monoclonal antibodies that could be used as carriers for a site-specific pharmacodelivery of cytotoxic drugs, cytokines or radionuclides to the BM in AML.
journal_name
Leukemiajournal_title
Leukemiaauthors
Angenendt L,Reuter S,Kentrup D,Benk AS,Neumann F,Hüve J,Martens AC,Schwöppe C,Kessler T,Schmidt LH,Sauer T,Brand C,Mikesch JH,Lenz G,Mesters RM,Müller-Tidow C,Hartmann W,Wardelmann E,Neri D,Berdel WE,Roesli C,Scdoi
10.1038/leu.2017.208subject
Has Abstractpub_date
2018-02-01 00:00:00pages
510-519issue
2eissn
0887-6924issn
1476-5551pii
leu2017208journal_volume
32pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::14-3-3 proteins are a family of master regulators of intracellular signaling, yet their impact on proteasome function is unknown. We demonstrate that 14-3-3ζ binds the 11S proteasome activator, limiting proteasome assembly and cellular capacity for protein degradation. To define the functional impact of 14-3-3ζ protea...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.288
更新日期:2018-03-01 00:00:00
abstract::Neutropenia-related fungal infections can be life-threatening despite antifungal therapy. We evaluated the role of recombinant granulocyte colony-stimulating factor (rG-CSF)-elicited white blood cell (WBC) transfusions in patients with neutropenia-related fungal infections. Adult patients with hematologic malignancies...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/sj.leu.2400811
更新日期:1997-10-01 00:00:00
abstract::The inv(16)(p13q22) chromosomal rearrangement associated with FAB M4Eo acute myeloid leukemia (AML) subtype is characterized by the presence of the CBFbeta/MYH11 fusion transcript that can be used to detect minimal residual disease (MRD). However, qualitative RT-PCR studies of MRD have so far produced conflicting resu...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402478
更新日期:2002-06-01 00:00:00
abstract::In all, 17 consecutive patients in hematological complete remission (HCR) of acute promyelocytic leukemia (APL) received allogeneic stem cell transplantation (SCT) from an HLA-identical sibling and were monitored by reverse transcriptase polymerase chain reaction of PML/RARalpha prior and after transplant. Median age ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403078
更新日期:2003-10-01 00:00:00
abstract::The optimal donor for a patient undergoing reduced-intensity stem cell transplantation remains a human leukocyte antigen (HLA)-matched relative. Alternative donors such as matched unrelated donors (MUDs), mismatched related donors (haploidentical), or unrelated umbilical cord blood (UCB) units have emerged as options ...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2404932
更新日期:2008-01-01 00:00:00
abstract::ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/leu.2017.65
更新日期:2017-10-01 00:00:00
abstract::We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencie...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402031
更新日期:2001-03-01 00:00:00
abstract::Ligation of CD40 on chronic lymphocytic leukemia (CLL) cells induces phenotypic and biochemical changes that facilitate CLL cell-T cell interactions and enhances the sensitivity of CLL cells to clearance by adaptive and innate immune-effector mechanisms. CLL cells can be transduced to express CD40 ligand (CD154) using...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2010.191
更新日期:2010-11-01 00:00:00
abstract::To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day, days 1-3; cytarabine 150 mg/m2/day, days 1-7; aclarubicin 12 mg/m2/day, days 1-7) as an induction therapy in the treatment of de novo acute myeloid leukemia (AML), 48 patients with newly diagnosed AML, aged 35 (14-57) years, were entered ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404287
更新日期:2006-08-01 00:00:00
abstract::Chromosomal breakpoints associated with malignancy are known to cluster at particular regions of the karyotype. Based on a review of the literature we have identified a novel leukaemia syndrome associated with translocations involving 8p11. This syndrome is distinct from the previously described translocation t(8;16)(...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1995-10-01 00:00:00
abstract::Housekeeping genes, particularly actin, tubulin, and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are widely used to estimate the amount and integrity of RNA in Northern blotting. In this work, the most reliable housekeeping gene for gene expression analysis of Hodgkin's disease (HD) lymph n...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::The occurrence of leukemia in a gene therapy trial for SCID-X1 has highlighted insertional mutagenesis as an adverse effect. Although retroviral integration near the T-cell acute lymphoblastic leukemia (T-ALL) oncogene LIM-only protein 2 (LMO2) appears to be a common event, it is unclear why LMO2 was preferentially ta...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404563
更新日期:2007-04-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) in children is often considered as a variant of acute myeloid leukemia (AML) and frequently treated as such. However, there are very few reported data on the outcome following AML treatment. We analyzed 20 consecutive cases of de novo MDS treated in Denmark according to the NOPHO AML pro...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::On activation, umbilical cord blood (UCB) CD4(+) T cells demonstrate reduced expression of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), whereas maintaining equivalent interleukin-2 (IL-2) levels, as compared with adult peripheral blood (PB) CD4(+) T cells. Nuclear factor of activated T cel...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2008.234
更新日期:2008-12-01 00:00:00
abstract::We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.101
更新日期:2016-10-01 00:00:00
abstract::Pretreatment cytogenetics is an important parameter for risk stratification and therapy approach in acute lymphoblastic leukemia (ALL). However, in up to 30% of cases, chromosome banding analysis (CBA) fails or reveals a normal karyotype. To characterize the subset of ALL with normal karyotype or failed CBA, we perfor...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2015.276
更新日期:2016-02-01 00:00:00
abstract::We established the continuous growth of WEHI-3B D+ cells in protein-free chemically defined F-12 medium by stepwise decreases in the concentration of fetal calf serum. This cell line, designated as WEHI-3B-Y1, has now been propagated in protein-free F-12 medium for 3 years. The population-doubling time of the cells in...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated t...
journal_title:Leukemia
pub_type: 杂志文章,随机对照试验
doi:10.1038/leu.2008.174
更新日期:2008-10-01 00:00:00
abstract::The aim was to determine the efficacy and safety of decitabine in the settings of relapse post-allogeneic progenitor cell transplantation or as part of the conditioning regimen. Three patients (two AML, one ALL) received single agent decitabine 1000 mg/m2 total dose) for treatment of relapse post-transplant (group 1)....
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to potently induce apoptosis in various malignant cells by inhibiting RNA synthesis and nuclear factor-κB activity. Previously, we showed that triptolide promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria-mediated path...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.246
更新日期:2012-03-01 00:00:00
abstract::Hematopoiesis is orchestrated by interactions between hematopoietic stem/progenitor cells (HSPCs) and stromal cells within bone marrow (BM) niches. Side population (SP) functionality is a major characteristic of HSPCs related to quiescence and resistance to drugs and environmental stresses. At steady state, SP cells a...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.256
更新日期:2014-04-01 00:00:00
abstract::Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia (GVL) effects determining transplant outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cell...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404892
更新日期:2007-10-01 00:00:00
abstract::The mechanisms by which non-oncogene bearing, slowly transforming T-cell-tropic retroviruses induce leukemia is not well understood. Viruses such as the murine radiation leukemia virus (RadLV) induce oncogenic transformation of T-cells in the thymus only in vivo and after a long latency. The capacity of RadLV to induc...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission t...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403126
更新日期:2003-11-01 00:00:00
abstract::Kinase inhibitors block proliferative signals in BCR-ABL1+ leukemic cells, but their capacity to induce apoptosis is poorly understood. Initial studies suggested that very brief exposure to kinase inhibitors was sufficient to induce apoptosis in chronic myeloid leukemia (CML) cells. However, flaws in this experimental...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2014.156
更新日期:2015-01-01 00:00:00
abstract::In order to investigate the frequency of HHV-8 in MM patients from another geographic location, we obtained fresh bone marrow (BM) biopsies from Turkish patients with MM (n = 21), monoclonal gammopathy of undetermined significance (MGUS) (n = 2), plasmacytoma (n = 1) with BM plasma cell infiltration, various hematolog...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402190
更新日期:2001-08-01 00:00:00
abstract::The flow cytometric detection of minimal residual disease (MRD) in precursor-B-acute lymphoblastic leukemias (precursor-B-ALL) mainly relies on the identification of minor leukemic cell populations that can be discriminated from their normal counterparts on the basis of phenotypic aberrancies observed at diagnosis. Th...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402150
更新日期:2001-08-01 00:00:00
abstract::Reciprocal rearrangements of the MLL gene are among the most common chromosomal abnormalities in both Acute Lymphoblastic and Myeloid Leukemia. The MLL gene, located on the 11q23 chromosomal band, is involved in more than 40 recurrent translocations. In the present study, we describe the development and validation of ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403439
更新日期:2004-09-01 00:00:00
abstract::Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were se...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::We have investigated the protective effect of human T-cell leukemia virus I (HTLV-I) immune globulin (HTLVIG) against HTLV-I in rabbits. HTLVIG containing 77 mg/ml of IgG was prepared from pooled plasma from seropositive healthy persons. In the first experiment, four groups (A, B, C, and D) of three rabbits were trans...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00