Abstract:
:Homologous recombination repair (HRR) protects cells from the lethal effect of spontaneous and therapy-induced DNA double-stand breaks. HRR usually depends on BRCA1/2-RAD51, and RAD52-RAD51 serves as back-up. To target HRR in tumor cells, a phenomenon called "synthetic lethality" was applied, which relies on the addiction of cancer cells to a single DNA repair pathway, whereas normal cells operate 2 or more mechanisms. Using mutagenesis and a peptide aptamer approach, we pinpointed phenylalanine 79 in RAD52 DNA binding domain I (RAD52-phenylalanine 79 [F79]) as a valid target to induce synthetic lethality in BRCA1- and/or BRCA2-deficient leukemias and carcinomas without affecting normal cells and tissues. Targeting RAD52-F79 disrupts the RAD52-DNA interaction, resulting in the accumulation of toxic DNA double-stand breaks in malignant cells, but not in normal counterparts. In addition, abrogation of RAD52-DNA interaction enhanced the antileukemia effect of already-approved drugs. BRCA-deficient status predisposing to RAD52-dependent synthetic lethality could be predicted by genetic abnormalities such as oncogenes BCR-ABL1 and PML-RAR, mutations in BRCA1 and/or BRCA2 genes, and gene expression profiles identifying leukemias displaying low levels of BRCA1 and/or BRCA2. We believe this work may initiate a personalized therapeutic approach in numerous patients with tumors displaying encoded and functional BRCA deficiency.
journal_name
Bloodjournal_title
Bloodauthors
Cramer-Morales K,Nieborowska-Skorska M,Scheibner K,Padget M,Irvine DA,Sliwinski T,Haas K,Lee J,Geng H,Roy D,Slupianek A,Rassool FV,Wasik MA,Childers W,Copland M,Müschen M,Civin CI,Skorski Tdoi
10.1182/blood-2013-05-501072subject
Has Abstractpub_date
2013-08-15 00:00:00pages
1293-304issue
7eissn
0006-4971issn
1528-0020pii
blood-2013-05-501072journal_volume
122pub_type
杂志文章相关文献
BLOOD文献大全abstract::Platelets are vital for hemostasis because they release their granule contents in response to vascular damage. Platelet exocytosis is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), whose interactions are governed by regulators, eg, Sec/Munc18 proteins. These proteins chape...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-05-430629
更新日期:2012-09-20 00:00:00
abstract::Six patients with relapsed hairy cell leukemia after splenectomy were treated with high-dose methotrexate and leucovorin rescue. Five patients had objective responses as determined by improved blood counts. In two of them, the response has continued for more than 14 and 44 months, respectively. Intensive treatment wit...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract::McCullough and colleagues show that problems with cord banking still exist. To improve the results of cord transplantations, more attention should be given to ensuring quality standards rather than just collecting more units. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2009-06-226738
更新日期:2009-08-20 00:00:00
abstract::To determine the clonal nature of hematopoiesis and to assess lineage involvement in patients with myelodysplastic syndromes (MDS), we used restriction fragment length polymorphisms of the X-linked genes phosphoglycerate kinase (PGK1) and hypoxanthine phosphoribosyltransferase (HPRT) and the X-linked probe M27 beta. E...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibalpha. Three polymorphisms have been described in GP Ibalpha (Kozak T/C polymorphism, variable number of tandem ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.1.36
更新日期:2001-07-01 00:00:00
abstract::The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood-2004-09-3728
更新日期:2005-07-01 00:00:00
abstract::In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in p...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2010-08-300863
更新日期:2011-03-17 00:00:00
abstract::Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available ...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2009-08-236356
更新日期:2010-04-08 00:00:00
abstract::Erythropoietin (EPO) is required for the survival and expansion of red blood cell progenitor cells and supports continued differentiation of these committed progenitors to mature red blood cells. After binding to its cognate receptor, EPO promotes receptor homodimerization, activation of receptor-associated JAK2, subs...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-10-15 00:00:00
abstract::The molecular determinants regulating the specification of human embryonic stem cells (hESCs) into hematopoietic cells remain elusive. HOXA9 plays a relevant role in leukemogenesis and hematopoiesis. It is highly expressed in hematopoietic stem and progenitor cells (HSPCs) and is downregulated upon differentiation. Ho...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-03-558825
更新日期:2014-11-13 00:00:00
abstract::HIV-1-associated thrombocytopenia (HIV-1-ITP) is a common complication of HIV-1 infection, frequently caused by increased peripheral platelet destruction mediated by antiplatelet antibodies (Abs) and/or platelet-bound immune complexes. Little is known about the specificity of the antiplatelet Abs at a molecular level....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-01-0386
更新日期:2004-12-15 00:00:00
abstract::Approximately 40% of children with acute myeloid leukemia (AML) who respond to initial therapy subsequently relapse. Multidimensional flow cytometry employing a standardized panel of monoclonal antibodies enables the detection of small numbers of occult leukemic cells that persist during therapy using technology adapt...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-10-3064
更新日期:2003-05-01 00:00:00
abstract::In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-02-268003
更新日期:2010-10-07 00:00:00
abstract::A strategy to phenotype rare populations of hematopoietic cells expressing the cell-surface marker CD34 was studied. The antigenic phenotype of umbilical core blood (CB) CD34+ cells was investigated using flow cytometry and compared with the mRNA-phenotype determined by cDNA-polymerase chain reaction (cDNA-PCR) analys...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::The pathogenesis of corticosteroid-resistant immune thrombocytopenia (ITP), a clinically challenging condition in which patients exhibit either no response to corticosteroids or are corticosteroid-dependent, remains poorly understood. Murine studies suggest that bone marrow (BM) endothelial progenitor cells (EPCs) pla...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2017-09-807248
更新日期:2018-03-15 00:00:00
abstract::CXCR4 chemokine receptors retain hematopoietic progenitors and leukemia cells within the marrow microenvironment. We prospectively evaluated the prognostic implication of CXCR4 in 90 consecutive patients with acute myelogenous leukemia (AML) by flow cytometry. Patients were divided into groups with low (n=32), interme...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-024844
更新日期:2007-01-15 00:00:00
abstract::Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-03-703819
更新日期:2016-08-25 00:00:00
abstract::Low concentrations of As(2)O(3) (=1 micromol/L) induce long-lasting remission in patients with acute promyelocytic leukemia (APL) without significant myelosuppressive side effects. Several groups, including ours, have shown that 0.5 to 1 micromol/L As(2)O(3) induces apoptosis in APL-derived NB4 cells, whereas other ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-09-15 00:00:00
abstract::Uncontrolled activation of the complement system against endothelial and blood cells is central to the pathogenesis of atypical hemolytic uremic syndrome (aHUS). aHUS patients frequently carry mutations in the inhibitory complement regulator factor H (FH). Mutations cluster in domains 19 and 20 (FH19-20), which are cr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-11-680009
更新日期:2016-06-02 00:00:00
abstract::We made a disease-specific comparison of unrelated cord blood (CB) recipients and human leukocyte antigen allele-matched unrelated bone marrow (BM) recipients among 484 patients with acute myeloid leukemia (AML; 173 CB and 311 BM) and 336 patients with acute lymphoblastic leukemia (ALL; 114 CB and 222 BM) who received...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2008-03-147041
更新日期:2009-02-19 00:00:00
abstract::Human herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. iMCD accou...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-10-746933
更新日期:2017-03-23 00:00:00
abstract::Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growt...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-022814
更新日期:2006-10-15 00:00:00
abstract::The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improv...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-04-423178
更新日期:2012-07-05 00:00:00
abstract::Circulating endothelial progenitor cells (EPCs) are thought to contribute to angiogenesis following vascular injury, stimulating interest in their ability to mediate therapeutic angiogenesis. However, the number of EPCs in the blood is low, limiting endogenous repair, and a method to rapidly mobilize EPCs has not been...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2006-06-030577
更新日期:2006-12-01 00:00:00
abstract::Fibrillar collagens are among the most potent activators of platelets and play an important role in the initiation of thrombosis. The glycoprotein VI (GPVI)/FcRgamma-chain complex is a central collagen receptor and inhibitors of GPVI produce a major defect in arterial thrombogenesis. In this study we have examined art...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4244
更新日期:2006-06-01 00:00:00
abstract::Meis1 is a homeodomain transcription factor coexpressed with Hoxa9 in most human acute myeloid leukemias (AMLs). In mouse models of leukemia produced by Hoxa9, Meis1 accelerates leukemogenesis. Because Hoxa9 immortalizes myeloid progenitors in the absence of Meis1 expression, the contribution of Meis1 toward leukemia ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-12-4664
更新日期:2005-07-01 00:00:00
abstract::Postthrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT) that reduces quality of life and has important socioeconomic consequences. More than one-third of patients with DVT will develop PTS, and 5% to 10% of patients will develop severe PTS, which may manifest as venous ulceration. The p...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2009-07-199174
更新日期:2009-11-19 00:00:00
abstract::We here report the initiation of hematopoietic recovery in congenitally hypoplastic S1/S1d mice by the cytotoxic ablation of cells bearing the natural killer (NK) phenotype (NK 1.1+). The most striking finding was the early several-fold increase in the cycling fraction of stem and progenitor cells (with the exception ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-09-15 00:00:00
abstract::Immune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-202655
更新日期:2009-08-06 00:00:00