Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}.

Abstract:

:PRKAR1A (R1A)-retinoic acid receptor-alpha (R1A-RARalpha) is the sixth RARalpha-containing fusion protein in acute promyelocytic leukemia (APL). Using the murine bone-marrow retroviral transduction/transformation assay, we showed that R1A-RARalpha fusion protein could transform bone-marrow progenitor/stem cells. In gel-shift assays, R1A-RARalpha was able to bind to a panel of retinoic acid response elements both as a homodimer and as a heterodimer with RXRalpha, and demonstrated distinct DNA-binding characteristics compared with wild-type RARalpha/RXRalpha or other X-RARalpha chimeric proteins. The ratio of R1A-RARalpha to RXRalpha proteins affected the retinoic acid response element interaction pattern of R1A-RARalpha/RXRalpha complexes. Studies comparing R1A-RARalpha with R1A-RARalpha(DeltaRIIa) demonstrated that the RIIa protein interaction domain located within R1A was responsible for R1A-RARalpha homodimeric DNA binding and interaction with wild-type R1A protein. However, the RIIa domain was not required for R1A-RARalpha-mediated transformation because its deletion in R1A-RARalpha(DeltaRIIa) did not compromise its transformation capability. In contrast, introduction of point mutations within the RARalpha portion of either R1A-RARalpha or R1A-RARalpha(DeltaRIIa), previously demonstrated to eliminate RXRalpha interaction or treatment of transduced cells with RXRalpha shRNA or a RXRalpha agonist, reduced transformation capability. Thus, leukemic transformation by APL fusion protein PRKAR1A-RARalpha is critically dependent on RXRalpha, which suggests RXRalpha is a promising target for APL.

journal_name

Blood

journal_title

Blood

authors

Qiu JJ,Lu X,Zeisig BB,Ma Z,Cai X,Chen S,Gronemeyer H,Tweardy DJ,So CW,Dong S

doi

10.1182/blood-2009-07-232652

subject

Has Abstract

pub_date

2010-01-21 00:00:00

pages

643-52

issue

3

eissn

0006-4971

issn

1528-0020

pii

blood-2009-07-232652

journal_volume

115

pub_type

杂志文章

相关文献

BLOOD文献大全
  • SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia.

    abstract::The Sox4 transcription factor mediates early B-cell differentiation. Compared with normal pre-B cells, SOX4 promoter regions in Ph(+) ALL cells are significantly hypomethylated. Loss and gain-of-function experiments identified Sox4 as a critical activator of PI3K/AKT and MAPK signaling in ALL cells. ChIP experiments c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-05-428938

    authors: Ramezani-Rad P,Geng H,Hurtz C,Chan LN,Chen Z,Jumaa H,Melnick A,Paietta E,Carroll WL,Willman CL,Lefebvre V,Müschen M

    更新日期:2013-01-03 00:00:00

  • MUC1-C oncoprotein suppresses reactive oxygen species-induced terminal differentiation of acute myelogenous leukemia cells.

    abstract::Acute myeloid leukemia (AML) cells are characterized by unlimited self-renewal and an impaired capacity to undergo terminal differentiation. The MUC1 oncoprotein is aberrantly expressed in AML cells; however, there has been no evidence for involvement of MUC1 in myeloid leukemogenesis. Cell-penetrating peptide inhibit...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-10-296632

    authors: Yin L,Wu Z,Avigan D,Rosenblatt J,Stone R,Kharbanda S,Kufe D

    更新日期:2011-05-05 00:00:00

  • Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells.

    abstract::The stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34(+) progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonoverlapping subsets of differentiating CD56(+) cells based on CD117 and ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-04-020198

    authors: Grzywacz B,Kataria N,Sikora M,Oostendorp RA,Dzierzak EA,Blazar BR,Miller JS,Verneris MR

    更新日期:2006-12-01 00:00:00

  • The interaction of platelets with aortic subendothelium: inhibition of adhesion and secretion by prostaglandin I2.

    abstract::We have studied the effect of prostaglandin I2 on platelet turnover, attachment to the subendothelium, and secretion following balloon deendothelialization of the rabbit aorta. Survival of 51Cr-labeled platelets in the balloon-injured animals remained normal. Thirty minutes after injury, there were 4.52 X 10(6) platel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Adelman B,Stemerman MB,Mennell D,Handin RI

    更新日期:1981-08-01 00:00:00

  • Pre-pre-B acute lymphoblastic leukemia: high frequency of alternatively spliced ALL1-AF4 transcripts and absence of minimal residual disease during complete remission.

    abstract::We used the polymerase chain reaction (PCR) to detect ALL1-AF4 rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre-pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias (ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of 12 children and 14 of 34 adults. Th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Janssen JW,Ludwig WD,Borkhardt A,Spadinger U,Rieder H,Fonatsch C,Hossfeld DK,Harbott J,Schulz AS,Repp R

    更新日期:1994-12-01 00:00:00

  • Immunotherapy with a posttranscriptionally modified DNA vaccine induces complete protection against metastatic neuroblastoma.

    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

    authors: Pertl U,Wodrich H,Ruehlmann JM,Gillies SD,Lode HN,Reisfeld RA

    更新日期:2003-01-15 00:00:00

  • Breaking barriers.

    abstract::It is difficult to imagine a greater challenge to the transplantation of haploidentical cells than thalassemia. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2009-11-254987

    authors: Woolfrey A

    更新日期:2010-02-11 00:00:00

  • Selective binding of the factor VIII/von Willebrand factor protein to human platelets.

    abstract::The factor VIII/von Willebrand factor protein was radiolabeled after modification by galactose oxidase and reduction with tritiated potassium borohydride. This mild efficient method for labeling resulted in retention of over 90% of the biologic activities of the factor VIII/von Willebrand factor protein. Binding of th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Morisato DK,Gralnick HR

    更新日期:1980-01-01 00:00:00

  • Safety of autologous, ex vivo-expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients.

    abstract::We infused six human immunodeficiency virus (HIV)-seropositive subjects with autologous CD8+ cytotoxic T cells (CTLs) enriched for HIV-specific cytotoxicity targeted against a diversity of HIV epitopes in gp120, gag p17 and p24, and nef. There was no toxicity and no subject deteriorated clinically. In the first 2 week...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:

    authors: Lieberman J,Skolnik PR,Parkerson GR 3rd,Fabry JA,Landry B,Bethel J,Kagan J

    更新日期:1997-09-15 00:00:00

  • Granulocyte-macrophage colony-stimulating factor mRNA stabilization enhances transgenic expression in normal cells and tissues.

    abstract::To increase transgenic production of granulocyte-macrophage colony-stimulating factor (GM-CSF), we mutated the mRNA's 3'-untranslated region, AUUUA instability elements. Expression vectors containing human or murine GM-CSF cDNAs coding for wild-type (GM-AUUUA) or mutant versions with reiterated AUGUA repeats (GM-AUGUA...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rajagopalan LE,Burkholder JK,Turner J,Culp J,Yang NS,Malter JS

    更新日期:1995-10-01 00:00:00

  • An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand.

    abstract::Identification of receptor activator of nuclear factor-kappaB (RANK) and RANK-ligand (RANKL) has provided new insights into the osteoclast differentiation pathway. Osteoclast precursor cells were isolated using monoclonal antibodies against c-Fms and RANK, and the effect of adherence on the in vitro differentiation an...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miyamoto T,Arai F,Ohneda O,Takagi K,Anderson DM,Suda T

    更新日期:2000-12-15 00:00:00

  • Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party.

    abstract::The median age of chronic myeloid leukemia (CML) patients is ~60 years, and age is still considered an important prognostic factor, included in Sokal and EURO risk scores. However, few data are available about the long-term outcome of older patients treated with imatinib (IM) frontline. We analyzed the relationship be...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-324228

    authors: Gugliotta G,Castagnetti F,Palandri F,Breccia M,Intermesoli T,Capucci A,Martino B,Pregno P,Rupoli S,Ferrero D,Gherlinzoni F,Montefusco E,Bocchia M,Tiribelli M,Pierri I,Grifoni F,Marzocchi G,Amabile M,Testoni N,Martin

    更新日期:2011-05-26 00:00:00

  • Correction of hypercoagulability and amelioration of pulmonary arterial hypertension by chronic blood transfusion in an asplenic hemoglobin E/beta-thalassemia patient.

    abstract::Chronic transfusion of packed red blood cells, in addition to other ongoing treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other supportive measures, was given to a splenectomized hemoglobin E/beta-thalassemia woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma thrombi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-09-3094

    authors: Atichartakarn V,Chuncharunee S,Chandanamattha P,Likittanasombat K,Aryurachai K

    更新日期:2004-04-01 00:00:00

  • Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo.

    abstract::Subsets of natural killer (NK) cells are characterized by the expression of inhibitory and/or stimulatory receptors specific for major histocompatibility complex (MHC) class I determinants. In mice, these include the Ly49 family of molecules. One mechanism by which tumor cells may evade NK cell killing is by expressin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.10.3132

    authors: Koh CY,Blazar BR,George T,Welniak LA,Capitini CM,Raziuddin A,Murphy WJ,Bennett M

    更新日期:2001-05-15 00:00:00

  • Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia.

    abstract::The purpose of this study was to determine the relative merits of idarubicin and daunorubicin in acute myeloid leukemia (AML) therapy. Thirty-two sites provided 214 previously untreated adults with AML aged 15 years or more who were randomized to receive for induction therapy cytarabine 100 mg/m2/d as a continuous 7-d...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Wiernik PH,Banks PL,Case DC Jr,Arlin ZA,Periman PO,Todd MB,Ritch PS,Enck RE,Weitberg AB

    更新日期:1992-01-15 00:00:00

  • Prognostic model for high-tumor-burden follicular lymphoma integrating baseline and end-induction PET: a LYSA/FIL study.

    abstract::Both total metabolic tumor volume (TMTV), computed on baseline positron emission tomography (PET), and end of induction (EOI) PET are imaging biomarkers showing promise for early risk stratification in patients with high-tumor-burden follicular lymphoma. A model was built incorporating these 2 factors in 159 patients ...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2017-11-816298

    authors: Cottereau AS,Versari A,Luminari S,Dupuis J,Chartier L,Casasnovas RO,Berriolo-Riedinger A,Menga M,Haioun C,Tilly H,Tarantino V,Federico M,Salles G,Trotman J,Meignan M

    更新日期:2018-05-31 00:00:00

  • Induction of proliferation and blast transformation by interferon in human malignant and non-malignant lymph node B cells.

    abstract::The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ostlund L,Biberfeld P,Robèrt KH,Christensson B,Einhorn S

    更新日期:1989-06-01 00:00:00

  • Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

    abstract::In patients with chronic myeloid leukemia, BCR-ABL mutations contribute to resistance to tyrosine kinase inhibitor therapy. We examined the occurrence of treatment-emergent mutations and their impact on response in patients from the ENESTnd phase 3 trial. At the 3-year data cutoff, mutations were detected in approxima...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2012-04-423418

    authors: Hochhaus A,Saglio G,Larson RA,Kim DW,Etienne G,Rosti G,De Souza C,Kurokawa M,Kalaycio ME,Hoenekopp A,Fan X,Shou Y,Kantarjian HM,Hughes TP

    更新日期:2013-05-02 00:00:00

  • CD4+ T-cell alloreactivity toward mismatched HLA class II alleles early after double umbilical cord blood transplantation.

    abstract::Although double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure compared with single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4+ T-ce...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2016-06-718619

    authors: Lamers CH,Wijers R,van Bergen CA,Somers JA,Braakman E,Gratama JW,Debets R,Falkenburg JH,Cornelissen JJ

    更新日期:2016-10-27 00:00:00

  • Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis.

    abstract::There is now strong experimental evidence that tissue factor pathway inhibitor (TFPI) is a critical inhibitor to modulate tissue factor-induced coagulation, but the role of TFPI as a risk factor for thrombosis is yet to be to be determined. This study investigated the role of low TFPI levels for the development of dee...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-10-3188

    authors: Dahm A,Van Hylckama Vlieg A,Bendz B,Rosendaal F,Bertina RM,Sandset PM

    更新日期:2003-06-01 00:00:00

  • Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma.

    abstract::Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) ...

    journal_title:Blood

    pub_type: 杂志文章,meta分析

    doi:10.1182/blood-2014-06-583369

    authors: Mir MA,Maurer MJ,Ziesmer SC,Slager SL,Habermann T,Macon WR,Link BK,Syrbu S,Witzig T,Friedberg JW,Press O,LeBlanc M,Cerhan JR,Novak A,Ansell SM

    更新日期:2015-02-05 00:00:00

  • High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetics.

    abstract::Inactivation of the retinoblastoma tumor-suppressor gene (RB-1) has been associated with tumorigenicity in various human malignancies. In chronic lymphoid leukemias of B-cell origin (B-CLL) an involvement of RB-1 has been suggested based on cytogenetic data. We examined RB-1 and its chromosomal locus 13q14 in 35 cases...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Stilgenbauer S,Döhner H,Bulgay-Mörschel M,Weitz S,Bentz M,Lichter P

    更新日期:1993-04-15 00:00:00

  • Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment.

    abstract::Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical tri...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2017-07-792143

    authors: Issa GC,Kantarjian HM,Gonzalez GN,Borthakur G,Tang G,Wierda W,Sasaki K,Short NJ,Ravandi F,Kadia T,Patel K,Luthra R,Ferrajoli A,Garcia-Manero G,Rios MB,Dellasala S,Jabbour E,Cortes JE

    更新日期:2017-11-09 00:00:00

  • Microsatellite instability and p53 mutations are associated with abnormal expression of the MSH2 gene in adult acute leukemia.

    abstract::Microsatellite instability (MSI) and p53 mutations have been reported to occur in a significant proportion of patients with therapy-related acute myeloid leukemia (AML). MSH2 is one of the genes involved in DNA mismatch repair to maintain fidelity of genomic replication, and defects of MSH2 are directly involved in MS...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zhu YM,Das-Gupta EP,Russell NH

    更新日期:1999-07-15 00:00:00

  • Murine malaria decreases hemopoietic stem cells.

    abstract::The causes of anemia and immunosuppression, major outcomes of malaria, are not well established. This study was undertaken to investigate whether erythropoietin (EP) production is adequate and whether the hemopoietic stem cells (CFU-S) were affected during the course of infection. Groups of female Balb/c mice infected...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Silverman PH,Schooley JC,Mahlmann LJ

    更新日期:1987-02-01 00:00:00

  • T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency.

    abstract::In common variable immunodeficiency (CVID) defects in early stages of B-cell development, bone marrow (BM) plasma cells and T lymphocytes have not been studied systematically. Here we report the first morphologic and flow cytometric study of B- and T-cell populations in CVID BM biopsies and aspirates. Whereas the hema...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-11-321695

    authors: Ochtrop ML,Goldacker S,May AM,Rizzi M,Draeger R,Hauschke D,Stehfest C,Warnatz K,Goebel H,Technau-Ihling K,Werner M,Salzer U,Eibel H,Schlesier M,Peter HH

    更新日期:2011-07-14 00:00:00

  • Hematopoietic bone marrow recovery after radiation therapy: MRI evaluation.

    abstract::Magnetic resonance imaging (MRI) is able to detect the increase of adipocytes in the hematopoietic bone marrow that occurs as a consequence of radiotherapy and is indicative of the loss of myeloid tissue. By monitoring this process, it is also possible to determine the recovery of the bone marrow. The amount of viable...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Casamassima F,Ruggiero C,Caramella D,Tinacci E,Villari N,Ruggiero M

    更新日期:1989-05-01 00:00:00

  • In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2.

    abstract::Identification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. To date, a homeobox transcription factor Hoxb4 has been only demonstrated to possess such an effect in mice. Here, we show that HSC-like cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-07-298596

    authors: Kitajima K,Minehata K,Sakimura K,Nakano T,Hara T

    更新日期:2011-04-07 00:00:00

  • Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population.

    abstract::Mast cells may be cultured from human peripheral blood in the presence of recombinant human stem cell factor (rhSCF). The characteristics of the cells in peripheral blood that give rise to mast cells are unknown. Because mast cell precursors in human marrow are CD34+, human peripheral blood mononuclear cells from pati...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rottem M,Okada T,Goff JP,Metcalfe DD

    更新日期:1994-10-15 00:00:00

  • High level engraftment of NOD/SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase.

    abstract::We have previously shown that intravenously injected peripheral blood (PB) or bone marrow (BM) cells from newly diagnosed chronic myeloid leukemia (CML) patients can engraft the BM of sublethally irradiated severe combined immunodeficient (SCID) mice. We now report engraftment results for chronic phase CML cells in no...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wang JC,Lapidot T,Cashman JD,Doedens M,Addy L,Sutherland DR,Nayar R,Laraya P,Minden M,Keating A,Eaves AC,Eaves CJ,Dick JE

    更新日期:1998-04-01 00:00:00