piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL.

Abstract:

:The initiation and progression of diffuse large B-cell lymphoma (DLBCL) is governed by genetic and epigenetic aberrations. As the most abundant eukaryotic message RNA modification, N6-methyladenosine (m6A) is known to influence various fundamental bioprocesses by regulating target gene; however, the function of m6A modifications in DLBCL is unclear. PIWI-interacting RNAs (piRNAs) have been indicated to be epigenetic effectors in cancer. Here, we show that high expression of piRNA-30473 supports the aggressive phenotype of DLBCL, and piRNA-30473 depletion decreases proliferation and induces cell cycle arrest in DLBCL cells. In xenograft DLBCL models, piRNA-30473 inhibition reduces tumor growth. Moreover, piRNA-30473 is significantly associated with overall survival (OS) in a univariate analysis, and is statistically significant after adjusting for the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in the multivariate analysis. Additional studies demonstrate that piRNA-30473 exerts its oncogenic role through a mechanism involving the upregulation of WTAP, an m6A mRNA methylase, thus enhances the global m6A level. Integrating transcriptome and m6A-seq analyses reveal that WTAP increases the expression of its critical target gene HK2 by enhancing the HK2 m6A level, thereby promoting the progression of DLBCL. Together, the piRNA-30473/WTAP/HK2 axis contributes to tumorigenesis by regulating m6A RNA methylation in DLBCL. Furthermore, by comprehensively analyzing our clinical data and datasets, we discover that the m6A regulatory genes piRNA-30473 and WTAP improve survival prediction in DLBCL patients. Our study highlights the functional importance of the m6A modification in DLBCL and might assist in the development of a prognostic stratification and therapeutic approach for DLBCL.

journal_name

Blood

journal_title

Blood

authors

Han H,Fan G,Song S,Jiang Y,Qian C,Zhang W,Su Q,Xue X,Zhuang W,Li B

doi

10.1182/blood.2019003764

subject

Has Abstract

pub_date

2020-09-23 00:00:00

eissn

0006-4971

issn

1528-0020

pii

463848

pub_type

杂志文章

相关文献

BLOOD文献大全
  • End-linked homodimers in fibrinogen Osaka VI with a B beta-chain extension lead to fragile clot structure.

    abstract::The authors have identified a 12-residue carboxyl-terminal extension of Lys-Ser-Pro-Met-Arg-Arg-Phe-Leu-Leu-Phe-Cys-Met in a dysfibrinogen derived from a woman heterozygotic for this abnormality and associated with severe bleeding. This extension is due to a T-to-A mutation that creates AAG encoding Lys at the stop (T...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sugo T,Nakamikawa C,Yoshida N,Niwa K,Sameshima M,Mimuro J,Weisel JW,Nagita A,Matsuda M

    更新日期:2000-12-01 00:00:00

  • Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients.

    abstract::In an international collaborative study, a central histologic review identified 891 patients with essential thrombocythemia, strictly defined by World Health Organization criteria. After a median follow-up of 6.2 years, 109 (12%) patients experienced arterial (n = 79) or venous (n = 37) thrombosis. In multivariable an...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2011-02-339002

    authors: Carobbio A,Thiele J,Passamonti F,Rumi E,Ruggeri M,Rodeghiero F,Randi ML,Bertozzi I,Vannucchi AM,Antonioli E,Gisslinger H,Buxhofer-Ausch V,Finazzi G,Gangat N,Tefferi A,Barbui T

    更新日期:2011-06-02 00:00:00

  • Hematopoietic cell transplantation and HIV cure: where we are and what next?

    abstract::The report of the so-called Berlin patient cured of HIV with hematopoietic stem cell transplantation and a few other studies raised tremendous hope, excitement, and curiosity in the field. The National Heart, Lung and Blood Institute of the National Institutes of Health convened a Working Group to address emerging hea...

    journal_title:Blood

    pub_type:

    doi:10.1182/blood-2013-07-518316

    authors: Zou S,Glynn S,Kuritzkes D,Shah M,Cook N,Berliner N,NHLBI AIDS Blood Session Working Group.

    更新日期:2013-10-31 00:00:00

  • Mycobacterium avium-intracellulare induces interleukin-6 from human monocytes and large granular lymphocytes.

    abstract::Mycobacterium avium-intracellulare (MAI) is an opportunistic pathogen commonly found in acquired immunodeficiency syndrome patients, whose immune systems are severely compromised. However, normal responses to this bacterium are apparently sufficient to prevent disseminated infection because disease is rarely found unl...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Blanchard DK,Michelini-Norris MB,Pearson CA,Freitag CS,Djeu JY

    更新日期:1991-05-15 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

  • Exposure of human megakaryocytes to high shear rates accelerates platelet production.

    abstract::Platelets originate from megakaryocytes (MKs) by cytoplasmic elongation into proplatelets. Direct platelet release is not seen in bone marrow hematopoietic islands. It was suggested that proplatelet fragmentation into platelets can occur intravascularly, yet evidence of its dependence on hydrodynamic forces is missing...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-03-209205

    authors: Dunois-Lardé C,Capron C,Fichelson S,Bauer T,Cramer-Bordé E,Baruch D

    更新日期:2009-08-27 00:00:00

  • Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML).

    abstract::Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-09-377044

    authors: Goodyear OC,Dennis M,Jilani NY,Loke J,Siddique S,Ryan G,Nunnick J,Khanum R,Raghavan M,Cook M,Snowden JA,Griffiths M,Russell N,Yin J,Crawley C,Cook G,Vyas P,Moss P,Malladi R,Craddock CF

    更新日期:2012-04-05 00:00:00

  • Granulocyte-macrophage colony-stimulating factor rescues TF-1 leukemia cells from ionizing radiation-induced apoptosis through a pathway mediated by protein kinase Calpha.

    abstract::Protein kinase C (PKC) activity has a recognized role in mediating apoptosis. However, the role of individual PKC isoforms in apoptosis is poorly defined. Therefore, we investigated the translocation of individual PKC isoforms during radiation-induced apoptosis with and without rescue from apoptosis by granulocyte-mac...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kelly ML,Tang Y,Rosensweig N,Clejan S,Beckman BS

    更新日期:1998-07-15 00:00:00

  • Erythrocyte-endothelial cell adherence in sickle cell disorders.

    abstract::Detachment of individual sickle erythrocytes from cultured endothelial cell monolayers has been evaluated by a fluid-shearing technique in an effort to quantitate adherence at shear forces that would be anticipated in the in vivo circulation. Nonirreversibly sickled cells (non-ISC) were more adherent at normal oxygen ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Smith BD,La Celle PL

    更新日期:1986-11-01 00:00:00

  • Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia.

    abstract::Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein-mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These pa...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1182/blood-2002-11-3419

    authors: Solary E,Drenou B,Campos L,de Crémoux P,Mugneret F,Moreau P,Lioure B,Falkenrodt A,Witz B,Bernard M,Hunault-Berger M,Delain M,Fernandes J,Mounier C,Guilhot F,Garnache F,Berthou C,Kara-Slimane F,Harousseau JL,Groupe O

    更新日期:2003-08-15 00:00:00

  • Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78.

    abstract::One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by mai...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:

    authors: Creutzig U,Ritter J,Riehm H,Langermann HJ,Henze G,Kabisch H,Niethammer D,Jürgens H,Stollmann B,Lasson U

    更新日期:1985-02-01 00:00:00

  • Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.

    abstract::The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ohara A,Kojima S,Hamajima N,Tsuchida M,Imashuku S,Ohta S,Sasaki H,Okamura J,Sugita K,Kigasawa H,Kiriyama Y,Akatsuka J,Tsukimoto I

    更新日期:1997-08-01 00:00:00

  • Sustained phenotypic correction of canine hemophilia A using an adeno-associated viral vector.

    abstract::Gene therapy for hemophilia A requires efficient delivery of the factor VIII gene and sustained protein expression at circulating levels of at least 1% to 2% of normal. Adeno-associated viral type 2 (AAV2) vectors have a number of advantages over other viral vectors, including an excellent safety profile and persisten...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-01-0292

    authors: Scallan CD,Lillicrap D,Jiang H,Qian X,Patarroyo-White SL,Parker AE,Liu T,Vargas J,Nagy D,Powell SK,Wright JF,Turner PV,Tinlin SJ,Webster SE,McClelland A,Couto LB

    更新日期:2003-09-15 00:00:00

  • Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies.

    abstract::The mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythemato...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Iuliano L,Praticò D,Ferro D,Pittoni V,Valesini G,Lawson J,FitzGerald GA,Violi F

    更新日期:1997-11-15 00:00:00

  • Evidence that growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells.

    abstract::Donor-matched transplantation of hematopoietic stem cells (HSCs) is widely used to treat hematologic malignancies but is associated with high mortality. The expansion of HSC numbers and their mobilization into the bloodstream could significantly improve therapy. We report here that adult mice conditionally deficient f...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-04-280305

    authors: Khandanpour C,Sharif-Askari E,Vassen L,Gaudreau MC,Zhu J,Paul WE,Okayama T,Kosan C,Möröy T

    更新日期:2010-12-09 00:00:00

  • Iron incorporation into ferritin and hemoglobin during differentiation of murine erythroleukemia cells.

    abstract::Hemoglobin and ferritin iron content have been followed during differentiation in tissue cultures of murine erythroleukemia cells (MELC) using the techniques of Mössbauer spectroscopy and electron microscopy. In undifferentiated cells grown without DMSO, only iron stored in ferritin was detected. The amount of iron in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ofer S,Fibach E,Kessel M,Bauminger ER,Cohen SG,Eikelboom J,Rachmilewitz EA

    更新日期:1981-08-01 00:00:00

  • Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia.

    abstract::The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow-up of 3.5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81% and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%, respect...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Fletcher JA,Lynch EA,Kimball VM,Donnelly M,Tantravahi R,Sallan SE

    更新日期:1991-02-01 00:00:00

  • A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma.

    abstract::Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regenera...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:

    authors: Link H,Boogaerts MA,Carella AM,Ferrant A,Gadner H,Gorin NC,Harabacz I,Harousseau JL,Hervé P,Holldack J

    更新日期:1992-11-01 00:00:00

  • Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide microarray.

    abstract::An imbalance between cellular apoptosis and survival may be critical for the pathogenesis of lymphoma. Therefore, the gene expression pattern in lymph node preparations from patients with mantle cell lymphoma (MCL) was compared to the pattern in nonmalignant hyperplastic lymph nodes (HLs). Oligonucleotide microarray a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.3.787

    authors: Hofmann WK,de Vos S,Tsukasaki K,Wachsman W,Pinkus GS,Said JW,Koeffler HP

    更新日期:2001-08-01 00:00:00

  • Human natural killer cell expansion is regulated by thrombospondin-mediated activation of transforming growth factor-beta 1 and independent accessory cell-derived contact and soluble factors.

    abstract::Natural killer cells (NK) were studied to determine factors important in their expansion. Flourescence-activated cell sorter (FACS) purified CD56+/CD3- NK cells cultured alone for 18 days in rIL-2 containing medium (1,000 U/mL) showed enhanced cytotoxicity but only minimal expansion. NK expansion was increased (12.5 +...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Pierson BA,Gupta K,Hu WS,Miller JS

    更新日期:1996-01-01 00:00:00

  • Gram-positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via Toll-like receptor activation.

    abstract::Although numerous studies have shown a higher risk of acquiring HIV infection in the presence of other sexually transmitted diseases, the biologic mechanisms responsible for enhanced HIV acquisition are unclear. Because Langerhans cells (LCs) are suspected to be the initial HIV targets after sexual exposure, we studie...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-10-185728

    authors: Ogawa Y,Kawamura T,Kimura T,Ito M,Blauvelt A,Shimada S

    更新日期:2009-05-21 00:00:00

  • How I treat acute lymphoblastic leukemia in older adolescents and young adults.

    abstract::At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggest...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2014-11-551481

    authors: Curran E,Stock W

    更新日期:2015-06-11 00:00:00

  • Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.

    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

    authors: Amadori S,Suciu S,Jehn U,Stasi R,Thomas X,Marie JP,Muus P,Lefrère F,Berneman Z,Fillet G,Denzlinger C,Willemze R,Leoni P,Leone G,Casini M,Ricciuti F,Vignetti M,Beeldens F,Mandelli F,De Witte T,EORTC\/GIMEMA Leukemi

    更新日期:2005-07-01 00:00:00

  • Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes.

    abstract::Plasmodium vivax merozoites only invade reticulocytes, a minor though heterogeneous population of red blood cell precursors that can be graded by levels of transferrin receptor (CD71) expression. The development of a protocol that allows sorting reticulocytes into defined developmental stages and a robust ex vivo P vi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-08-596015

    authors: Malleret B,Li A,Zhang R,Tan KS,Suwanarusk R,Claser C,Cho JS,Koh EG,Chu CS,Pukrittayakamee S,Ng ML,Ginhoux F,Ng LG,Lim CT,Nosten F,Snounou G,Rénia L,Russell B

    更新日期:2015-02-19 00:00:00

  • Prothrombin activation in blood coagulation: the erythrocyte contribution to thrombin generation.

    abstract::Prothrombin activation can proceed through the intermediates meizothrombin or prethrombin-2. To assess the contributions that these 2 intermediates make to prothrombin activation in tissue factor (Tf)-activated blood, immunoassays were developed that measure the meizothrombin antithrombin (mTAT) and α-thrombin antithr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-05-427856

    authors: Whelihan MF,Zachary V,Orfeo T,Mann KG

    更新日期:2012-11-01 00:00:00

  • Electrolyte and acid-base disturbances in the management of leukemia.

    abstract::Electrolyte disturbances in leukemia can be the result of the disease process or drug therapy. One group of electrolyte abnormalities is related to the stage of the leukemic process. Included in this group are newly diagnosed patients who may show elevated serum potassium, phosphorus, and magnesium--a result of their ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: O'Regan S,Carson S,Chesney RW,Drummond KN

    更新日期:1977-03-01 00:00:00

  • Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 expression in monocyte-derived dendritic cells.

    abstract::Patients after allogeneic stem-cell transplantation (alloSCT) have an increased risk for invasive aspergillosis (IA). Here, recipients of an allograft with IA (n=81) or without IA (n=58) were screened for 84 single nucleotide polymorphisms in 18 immune relevant genes. We found 3 markers in chemokine (C-X-C motif) liga...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2007-05-090928

    authors: Mezger M,Steffens M,Beyer M,Manger C,Eberle J,Toliat MR,Wienker TF,Ljungman P,Hebart H,Dornbusch HJ,Einsele H,Loeffler J

    更新日期:2008-01-15 00:00:00

  • Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.

    abstract::Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large vo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Moake JL,Turner NA,Stathopoulos NA,Nolasco L,Hellums JD

    更新日期:1988-05-01 00:00:00

  • Harvesting and enrichment of hematopoietic progenitor cells mobilized into the peripheral blood of normal donors by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation.

    abstract::To explore the use of stem/progenitor cells from peripheral blood (PB) for allogeneic transplantation, we have studied the mobilization of progenitor cells in normal donors by growth factors. Normal subjects were administered either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 10 micrograms/kg/d, or G-...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lane TA,Law P,Maruyama M,Young D,Burgess J,Mullen M,Mealiffe M,Terstappen LW,Hardwick A,Moubayed M

    更新日期:1995-01-01 00:00:00

  • Complex formation with pentraxin-2 regulates factor X plasma levels and macrophage interactions.

    abstract::Recently, we have identified scavenger receptor class A member I (SR-AI) as a receptor for coagulation factor X (FX), mediating the formation of an FX reservoir at the macrophage surface. Here, we demonstrate that the FX/SR-AI-complex comprises a third protein, pentraxin-2 (PTX2). The presence of PTX2 is essential to ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-06-724351

    authors: Muczynski V,Aymé G,Regnault V,Vasse M,Borgel D,Legendre P,Bazaa A,Harel A,Loubière C,Lenting PJ,Denis CV,Christophe OD

    更新日期:2017-04-27 00:00:00