Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors.

Abstract:

:The MLL gene located at 11q23 is frequently disrupted by chromosomal translocation in a wide spectrum of newly diagnosed acute leukemias. Recently, it has become apparent that the MLL gene is very frequently disrupted by chromosomal translocations in patients with secondary leukemias associated with chemotherapeutic regimens incorporating topoisomerase II inhibitors. These secondary leukemias associated with topoisomerase II inhibitors (most commonly teniposide, etoposide, or doxorubicin) have distinct clinical and biologic features which have led to the speculation that they are induced by treatment with topoisomerase II inhibitors. We have identified a site within the MLL breakpoint cluster region (bcr) that is highly sensitive to double-strand DNA cleavage induced by topoisomerase II inhibitors. This finding is quite specific and highly reproducible. Although it was initially discovered in malignant lymphoblasts isolated from a patient receiving multiagent chemotherapy, this site-specific double-strand DNA cleavage can be induced in tissue culture using malignant cell lines as well as peripheral blood from normal individuals. Site-specific cleavage occurs in a significant fraction of cells using a variety of model systems, is both time and dose dependent, and can be induced with either doxorubicin or etoposide. This site-specific cleavage maps to the same region as a consensus topoisomerase II cleavage site within the MLL bcr. These results suggest that site specific cleavage within the MLL bcr induced by topoisomerase II inhibitors may be an early step leading to MLL translocations and secondary leukemia.

journal_name

Blood

journal_title

Blood

authors

Aplan PD,Chervinsky DS,Stanulla M,Burhans WC

subject

Has Abstract

pub_date

1996-04-01 00:00:00

pages

2649-58

issue

7

eissn

0006-4971

issn

1528-0020

journal_volume

87

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Hereditary abnormality of platelet aggregation attributable to nucleotide storage pool deficiency.

    abstract::An abnormality of platelet aggregation has been detected in six family members with mild bleeding tendencies. In citrated platelet-rich plasma, primary aggregation induced by ADP or epinephrine and agglutination in response to ristocetin were present but second wave aggregation and aggregation in response to collagen ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ingerman CM,Smith JB,Shapiro S,Sedar A,Silver MJ

    更新日期:1978-08-01 00:00:00

  • Cell-surface heparan sulfate proteoglycan-mediated regulation of human neutrophil migration by the serpin antithrombin III.

    abstract::The serpin antithrombin III (AT III) is reported to have hemostasis-regulating and anti-inflammatory properties. To determine its ability to influence thrombin-independent leukocyte responses, the direct effects of the AT III concentrate Kybernin P and a monoclonal antibody-purified AT III on neutrophil migration were...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.4.1079

    authors: Dunzendorfer S,Kaneider N,Rabensteiner A,Meierhofer C,Reinisch C,Römisch J,Wiedermann CJ

    更新日期:2001-02-15 00:00:00

  • Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3.

    abstract::Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as being induced by a variety of environmental stresses such as osmotic shock, ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1). We found that the hematopoietic cytokine...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nagata Y,Moriguchi T,Nishida E,Todokoro K

    更新日期:1997-08-01 00:00:00

  • Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program.

    abstract::Granzyme H (GzmH) belongs to a family of 5 human serine proteases that are expressed by cytotoxic immune effector cells. Although GzmH is most closely related to the caspase-activating granzyme B (GzmB), neither a natural substrate nor a role in immune defense reactions has been demonstrated for this orphan granzyme. ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-10-051649

    authors: Fellows E,Gil-Parrado S,Jenne DE,Kurschus FC

    更新日期:2007-07-15 00:00:00

  • Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia.

    abstract::Human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia (ATL), a fatal T-cell leukemia resistant to chemotherapy, after more than 50 years of clinical latency from transmission through breast-feeding. Polyclonal expansion of virus-infected T cells predisposes them to transformation. Constitutive activ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-09-3646

    authors: Watanabe M,Ohsugi T,Shoda M,Ishida T,Aizawa S,Maruyama-Nagai M,Utsunomiya A,Koga S,Yamada Y,Kamihira S,Okayama A,Kikuchi H,Uozumi K,Yamaguchi K,Higashihara M,Umezawa K,Watanabe T,Horie R

    更新日期:2005-10-01 00:00:00

  • Characterization of nuclear factors that bind to a critical positive regulatory element of the human granulocyte-macrophage colony-stimulating factor promoter.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates the proliferation, maturation, and functional activity of myeloid cells in peripheral blood and bone marrow. Expression of GM-CSF is tightly regulated and is limited to cells stimulated directly (T cells, macroph...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Fraser JK,Tran S,Nimer SD,Gasson JC

    更新日期:1994-10-15 00:00:00

  • AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases.

    abstract::Acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene comprise one category of recurring genetic abnormalities in the WHO classification. In an unselected series of 1897 AML cases, 54 patients with an 11q23/MLL rearrangement were identified, resulting in an incidence of 2.8%. The incidence...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-02-0434

    authors: Schoch C,Schnittger S,Klaus M,Kern W,Hiddemann W,Haferlach T

    更新日期:2003-10-01 00:00:00

  • Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses.

    abstract::The tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-02-075945

    authors: Hipp MM,Hilf N,Walter S,Werth D,Brauer KM,Radsak MP,Weinschenk T,Singh-Jasuja H,Brossart P

    更新日期:2008-06-15 00:00:00

  • Platelet adhesion involves a novel interaction between vimentin and von Willebrand factor under high shear stress.

    abstract::The interaction between platelet receptor glycoprotein Ibα and the A1 domain of von Willebrand factor (VWF) mediates tethering/translocation of platelets to sites of vascular injury. Unexpectedly, we observed platelets translocating over A1A2A3 domains protein slower than on A1 domain at high shear stress. This observ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-10-530428

    authors: Da Q,Behymer M,Correa JI,Vijayan KV,Cruz MA

    更新日期:2014-04-24 00:00:00

  • The carboxyterminal EF domain of erythroid alpha-spectrin is necessary for optimal spectrin-actin binding.

    abstract::Spectrin and protein 4.1R crosslink F-actin, forming the membrane skeleton. Actin and 4.1R bind to one end of β-spectrin. The adjacent end of α-spectrin, called the EF domain, is calmodulin-like, with calcium-dependent and calcium-independent EF hands. The severely anemic sph(1J)/sph(1J) mouse has very fragile red cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-12-260612

    authors: Korsgren C,Lux SE

    更新日期:2010-10-07 00:00:00

  • The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

    abstract::We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Carroll AJ,Crist WM,Link MP,Amylon MD,Pullen DJ,Ragab AH,Buchanan GR,Wimmer RS,Vietti TJ

    更新日期:1990-09-15 00:00:00

  • Thrombopoietin initiates demethylation-based transcription of GP6 during megakaryocyte differentiation.

    abstract::Glycoprotein VI (GPVI) is an essential platelet receptor for collagens that is exclusively expressed in the megakaryocytic lineage. Transcription of the human gene GP6 is driven largely by GATA-binding protein 1 (GATA-1), specificity protein 1 (Sp1), and Friend leukemia integration 1 (Fli-1). In this report, we show t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-08-3109

    authors: Kanaji S,Kanaji T,Jacquelin B,Chang M,Nugent DJ,Komatsu N,Moroi M,Izuhara K,Kunicki TJ

    更新日期:2005-05-15 00:00:00

  • International scoring system for evaluating prognosis in myelodysplastic syndromes.

    abstract::Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical da...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Greenberg P,Cox C,LeBeau MM,Fenaux P,Morel P,Sanz G,Sanz M,Vallespi T,Hamblin T,Oscier D,Ohyashiki K,Toyama K,Aul C,Mufti G,Bennett J

    更新日期:1997-03-15 00:00:00

  • Phosphorylation of protein 4.1 in Plasmodium falciparum-infected human red blood cells.

    abstract::The composition of the erythrocyte plasma membrane is extensively modified during the intracellular growth of the malaria parasite Plasmodium falciparum. It has been previously shown that an 80-kD phosphoprotein is associated with the plasma membrane of human red blood cells (RBCs) infected with trophozoite/schizont s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chishti AH,Maalouf GJ,Marfatia S,Palek J,Wang W,Fisher D,Liu SC

    更新日期:1994-06-01 00:00:00

  • Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers.

    abstract::An immune pathophysiology for acquired aplastic anemia (AA) has been inferred from the responsiveness of the patients to immunosuppressive therapies and experimental laboratory data. To address the transcriptome of hematopoietic cells in AA, we undertook GeneChip analysis of the extremely limited numbers of progenitor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-02-0490

    authors: Zeng W,Chen G,Kajigaya S,Nunez O,Charrow A,Billings EM,Young NS

    更新日期:2004-01-01 00:00:00

  • Sex related differences in platelet function: the effect of aspirin.

    abstract::There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromb...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kelton JG,Carter CJ,Santos A,Hirsh J

    更新日期:1982-03-01 00:00:00

  • Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype.

    abstract::Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-11-679902

    authors: Toubiana J,Okada S,Hiller J,Oleastro M,Lagos Gomez M,Aldave Becerra JC,Ouachée-Chardin M,Fouyssac F,Girisha KM,Etzioni A,Van Montfrans J,Camcioglu Y,Kerns LA,Belohradsky B,Blanche S,Bousfiha A,Rodriguez-Gallego C,Meyts

    更新日期:2016-06-23 00:00:00

  • Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells.

    abstract::The plasma membrane calcium pump (PMCA) is the only active Ca2+ transporter in human red blood cells (RBCs). Previous measurements of maximal Ca2+ extrusion rates (Vmax) reported only mean values in the RBC population. Despite early evidence for differences in Ca2+ extrusion capacity among RBCs, the precise Vmax distr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-06-1787

    authors: Lew VL,Daw N,Perdomo D,Etzion Z,Bookchin RM,Tiffert T

    更新日期:2003-12-01 00:00:00

  • Growth of clonogenic myeloblastic leukemic cells in the presence of human recombinant erythropoietin in addition to various human recombinant hematopoietic growth factors.

    abstract::The effects of human recombinant erythropoietin (rEpo) in the presence of other stimulators on the growth of clonogenic leukemic blast cells from ten Japanese patients with acute myeloblastic leukemia were studied with an in vitro leukemic blast colony assay in methylcellulose culture. With the addition of rEpo alone,...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Asano Y,Okamura S,Shibuya T,Harada M,Niho Y

    更新日期:1988-11-01 00:00:00

  • Thrombosis in primary myelofibrosis: incidence and risk factors.

    abstract::We assessed frequency and predictive factors for major cardiovascular (CV) events in 707 patients with primary myelofibrosis (PMF) followed in 4 European institutions. A total of 236 deaths (33%) were recorded for an overall mortality of 7.7% patient-years (pt-yr). Fatal and nonfatal thromboses were registered in 51 (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-08-238956

    authors: Barbui T,Carobbio A,Cervantes F,Vannucchi AM,Guglielmelli P,Antonioli E,Alvarez-Larrán A,Rambaldi A,Finazzi G,Barosi G

    更新日期:2010-01-28 00:00:00

  • A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype.

    abstract::The Duffy blood group system is of clinical and biological significance. Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease. The Duffy protein is a receptor for the Plasmodium vivax erythrocyte-binding protein and is also a receptor for various chem...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Parasol N,Reid M,Rios M,Castilho L,Harari I,Kosower NS

    更新日期:1998-10-01 00:00:00

  • von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke.

    abstract::Stroke is a leading cause of death and disability. The only therapy available is recombinant tissue plasminogen activator, but side effects limit its use. Platelets play a crucial role during stroke, and the inflammatory reaction promotes neurodegeneration. von Willebrand factor (VWF), an adhesion molecule for platele...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-03-213264

    authors: Zhao BQ,Chauhan AK,Canault M,Patten IS,Yang JJ,Dockal M,Scheiflinger F,Wagner DD

    更新日期:2009-10-08 00:00:00

  • STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90alpha and beta in multiple myeloma cells, which critically contribute to tumor-cell survival.

    abstract::The combined blockade of the IL-6R/STAT3 and the MAPK signaling pathways has been shown to inhibit bone marrow microenvironment (BMM)-mediated survival of multiple myeloma (MM) cells. Here, we identify the molecular chaperones heat shock proteins (Hsp) 90alpha and beta as target genes of both pathways. The siRNA-media...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-05-024372

    authors: Chatterjee M,Jain S,Stühmer T,Andrulis M,Ungethüm U,Kuban RJ,Lorentz H,Bommert K,Topp M,Krämer D,Müller-Hermelink HK,Einsele H,Greiner A,Bargou RC

    更新日期:2007-01-15 00:00:00

  • Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b.

    abstract::Lymphomatoid granulomatosis (LyG) is an angiodestructive lymphoproliferative disorder (LPD) often involving the lungs. Its etiology is uncertain, but a number of previous studies had suggested it is a T-cell LPD associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymp...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wilson WH,Kingma DW,Raffeld M,Wittes RE,Jaffe ES

    更新日期:1996-06-01 00:00:00

  • Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta-chain gene causing activation of cryptic splice sites.

    abstract::Congenital afibrinogenemia is a rare inherited coagulopathy, characterized by very low or unmeasurable plasma levels of immunoreactive fibrinogen. So far, 25 mutations have been identified in afibrinogenemia, 17 in the Aalpha, 6 in the gamma, and only 2 in the Bbeta fibrinogen-chain genes. Here, 2 afibrinogenemic prob...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-06-1647

    authors: Spena S,Duga S,Asselta R,Malcovati M,Peyvandi F,Tenchini ML

    更新日期:2002-12-15 00:00:00

  • Cytokine-induced selective expansion and maturation of erythroid versus myeloid progenitors from purified cord blood precursor cells.

    abstract::To study the role of different cytokine combinations on the proliferation and differentiation of highly purified primitive progenitor cells, a serum-free liquid culture system was used in combination with phenotypic and functional analysis of the cells produced in culture. CD34+ CD45RAlo CD71lo cells, purified from um...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Mayani H,Dragowska W,Lansdorp PM

    更新日期:1993-06-15 00:00:00

  • Human erythroid progenitor cells express Rhesus antigens.

    abstract::The expression of Rhesus antigens on hematopoietic progenitor cells was studied using monoclonal antibodies. Because these antibodies are not capable of lysing mature red blood cells in a complement-dependent cytotoxicity assay, fluorescence-activated cell sorting was performed. Using the monoclonal anti-Rh 29 antibod...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Falkenburg JH,Fibbe WE,van der Vaart-Duinkerken N,Nichols ME,Rubinstein P,Jansen J

    更新日期:1985-09-01 00:00:00

  • Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia.

    abstract::A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly ant...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Gmür J,von Felten A,Osterwalder B,Honegger H,Hörmann A,Sauter C,Deubelbeiss K,Berchtold W,Metaxas M,Scali G,Frick PG

    更新日期:1983-08-01 00:00:00

  • alpha-Actinin and vinculin in normal and thrombasthenic platelets.

    abstract::Recently, the contractile protein alpha-actinin was identified in normal human platelets by its antigenic cross-reaction with a monospecific antibody to purified muscle alpha-actinin. In this study, we extend that preliminary identification of platelet alpha-actinin. Amino acid analysis, one-dimensional peptide maps, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Langer BG,Gonnella PA,Nachmias VT

    更新日期:1984-03-01 00:00:00

  • HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis.

    abstract::The mechanisms of CD4(+) T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4(+) T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4(+) T-cell levels probably d...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-01-331306

    authors: Sauce D,Larsen M,Fastenackels S,Pauchard M,Ait-Mohand H,Schneider L,Guihot A,Boufassa F,Zaunders J,Iguertsira M,Bailey M,Gorochov G,Duvivier C,Carcelain G,Kelleher AD,Simon A,Meyer L,Costagliola D,Deeks SG,Lambotte

    更新日期:2011-05-12 00:00:00