Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia.

Abstract:

BACKGROUND AND OBJECTIVES:Aberrant promoter methylation targets CpG islands causing gene silencing. We explored aberrant promoter methylation of genes potentially involved in B-cell malignancies and encoding proteins implicated in DNA repair (O6-methylguanine-DNA methyltransferase, MGMT), detoxification of environmental xenobiotics (glutathione S-transferase P1, GSTP1), apoptosis regulation (death associated protein kinase, DAP-k and caspase 8, CASP8) and cell cycle control (p73). DESIGN AND METHODS:Three hundred and seventeen B-cell malignancies were investigated by methylation-specific polymerase chain reaction (MSP) of MGMT, GSTP1, DAP-k, CASP8 and p73 genes. In selected cases, MSP results were matched to protein expression studies by immunohistochemistry or Western blotting. RESULTS:DAP-k promoter methylation occurred at highest frequency in follicular lymphoma (85.0%) and MALT-lymphoma (72.2%). MGMT methylation targeted both precursor B-cell neoplasia (23.8%) and mature B-cell tumors (27.6%). GSTP1 methylation was commonest in hairy cell leukemia (75.0%), follicular lymphoma (55.5%), Burkitt s lymphoma (52.0%), and MALT lymphoma (50.0%). Methylation of p73 and CASP8 was rare or absent. DAP-k and MGMT methylation caused absent protein expression. INTERPRETATION AND CONCLUSIONS:Methylation of MGMT, DAP-k and GSTP1 represents a major pathogenetic event in several B-cell malignancies. In follicular lymphoma and MALT lymphoma, frequent inactivation of the apoptosis extrinsic pathway through DAP-k methylation may reinforce the survival advantage already conferred by deregulation of the intrinsic apoptotic pathway. Inactivation of GSTP1 in gastric MALT lymphoma represents an additional mechanism favoring accumulation of reactive oxygen species and lymphomagenesis. Finally, the frequency of GSTP1 aberrant methylation in diffuse large B-cell lymphoma prompts studies aimed at verifying the prognostic impact of this epigenetic lesion in these lymphomas.

journal_name

Haematologica

journal_title

Haematologica

authors

Rossi D,Capello D,Gloghini A,Franceschetti S,Paulli M,Bhatia K,Saglio G,Vitolo U,Pileri SA,Esteller M,Carbone A,Gaidano G

keywords:

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

154-64

issue

2

eissn

0390-6078

issn

1592-8721

journal_volume

89

pub_type

杂志文章
  • The longest surviving child with Hoyeraal-Hreidarsson Syndrome.

    abstract::We describe the case of a 12-year old boy with Hoyeraal-Hreidarsson Syndrome (HHS). This syndrome includes intrauterine growth retardation, microcephaly, mental retardation, cerebellar malformation, and pancytopenia. HHS is a severe multisystem disorder associated with premature mortality, due to bone marrow failure. ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Ozdemir MA,Karakukcu M,Kose M,Kumandas S,Gumus H

    更新日期:2004-09-01 00:00:00

  • Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin's lymphoma.

    abstract:BACKGROUND:Classical Hodgkin's lymphoma is characterized by a minority of neoplastic cells surrounded by a heterogeneous background population of non-neoplastic cells including lymphoma-associated macrophages. High levels of expression of both the monocyte/macrophage lineage-associated antigens CD68 and CD163 have been...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2010.031542

    authors: Kamper P,Bendix K,Hamilton-Dutoit S,Honoré B,Nyengaard JR,d'Amore F

    更新日期:2011-02-01 00:00:00

  • Hemophilia therapy: the future has begun.

    abstract::The success story of hemophilia care first began in the 1970s, when the availability of plasma-derived concentrates of coagulation factor VIII (FVIII) and factor IX (FIX) provided efficacious treatment of bleeding in patients with hemophilia A and B. This positive scenario was consolidated in terms of greater safety a...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2019.232132

    authors: Mannucci PM

    更新日期:2020-03-01 00:00:00

  • Primary gastric non-Hodgkin's lymphoma in a population-based registry.

    abstract:BACKGROUND:The incidence of primary gastric non-Hodgkin's lymphoma (NHL) appears to have increased worldwide in recent years, and this seems to be confirmed by large-sample population studies. METHODS AND RESULTS:We derived our data from the Lombardy Cancer Registry, which provides the incidence of cancer in the provi...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Pinotti G,Novario R,Berrino F,Bianchi P,Comi MA,Gamba MC,Venco A

    更新日期:1992-09-01 00:00:00

  • Simultaneous occurrence of B-cell chronic lymphocytic leukemia and chronic myeloid leukemia with further evolution to lymphoid blast crisis.

    abstract::The coexistence of chronic myeloid leukemia (CML) and B-cell chronic lymphocytic leukemia (CLL) in the same patient is rare. A 71-year-old woman developed a B-lineage lymphoid blast crisis at 18 months after diagnosis of Ph-positive CML. At this time, a lymphoid cell population with morphologic and immunophenotypic fe...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:

    authors: Esteve J,Cervantes F,Rives S,Rozman M,Zarco MA,Montserrat E

    更新日期:1997-09-01 00:00:00

  • Limited value of FLT3 mRNA expression in the bone marrow for prognosis and monitoring of patients with acute myeloid leukemia.

    abstract::We studied wild-type FLT3 mRNA expression at diagnosis in bone marrow samples from 85 patients with acute myeloid leukemia (AML), 23 of whom were in complete remission, and determined its utility as a marker for minimal residual disease (MRD). We conclude that FLT3 expression is of limited value as a prognostic marker...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Kainz B,Fonatsch C,Schwarzinger I,Sperr WR,Jäger U,Gaiger A

    更新日期:2005-05-01 00:00:00

  • Survival for older patients with acute myeloid leukemia: a population-based study.

    abstract:BACKGROUND:Acute myeloid leukemia is the second most common leukemia among United States adults with a median age of 69 years. We investigated recent clinical practices related to treatments and disease outcomes in older patients with acute myeloid leukemia in the United States. DESIGN AND METHODS:In this retrospectiv...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2012.066100

    authors: Oran B,Weisdorf DJ

    更新日期:2012-12-01 00:00:00

  • Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis.

    abstract::Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 pat...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:10.3324/haematol.2015.128025

    authors: Sachchithanantham S,Offer M,Venner C,Mahmood SA,Foard D,Rannigan L,Lane T,Gillmore JD,Lachmann HJ,Hawkins PN,Wechalekar AD

    更新日期:2015-11-01 00:00:00

  • Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores the angiogenic homeostasis and suppresses tumor progression.

    abstract::Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases in the bone marrow (BM), we investigated whether BM MM endothelial cells (MMECs) control disease progression vi...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2019.239913

    authors: Solimando AG,Da Vià MC,Leone P,Borrelli P,Croci GA,Tabares P,Brandl A,Di Lernia G,Bianchi FP,Tafuri S,Steinbrunn T,Balduini A,Melaccio A,De Summa S,Argentiero A,Rauert-Wunderlich H,Frassanito MA,Ditonno P,Henke E,Kl

    更新日期:2020-04-30 00:00:00

  • Phosphotyrosine proteins in platelets from patients with storage pool disease: direct relation between granule defects and defective signal transduction.

    abstract:BACKGROUND AND OBJECTIVES:Storage pool diseases (SPD) are heterogeneous disorders associated with an abnormal presence of intraplatelet granules, which cause mild to moderate bleeding diathesis. We investigated signaling through tyrosine phosphorylation of proteins occurring in platelets with total or partial absence o...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Arderiu G,Díaz-Ricart M,Domenech P,Escolar G,Ordinas A,Pujol-Moix N

    更新日期:2002-06-01 00:00:00

  • Autologous transplantation in multiple myeloma: a GITMO retrospective analysis on 290 patients. Gruppo Italiano Trapianti di Midollo Osseo.

    abstract:BACKGROUND AND OBJECTIVE:Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions w...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Majolino I,Vignetti M,Meloni G,Vegna ML,Scimè R,Tringali S,Amaddii G,Coser P,Tribalto M,Raimondi R,Bergonzi C,Sajeva MR,Sica S,Ferrando F,Messina G,Mandelli F

    更新日期:1999-09-01 00:00:00

  • Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    abstract::Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this disorder and showe...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:10.3324/haematol.2011.045179

    authors: Darghouth D,Koehl B,Heilier JF,Madalinski G,Bovee P,Bosman G,Delaunay J,Junot C,Roméo PH

    更新日期:2011-12-01 00:00:00

  • Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukemia in patients over 60 years old. Results of the CETLAM AML-99 protocol.

    abstract:BACKGROUND AND OBJECTIVES:The benefits of high-dose cytarabine, anthracyclines and hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia (AML) are greater in younger rather than in older patients. We assessed the proportion of patients over 60 years with de novo AML who qualified for intens...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Oriol A,Ribera JM,Esteve J,Guàrdia R,Brunet S,Bueno J,Pedro C,Llorente A,Tormo M,Besalduch J,Sánchez JM,Batlle M,Vivancos P,Carreras E,Vilà JM,Julià A,Sierra J,Montserrat E,Feliu E,CETLAM AML-99.

    更新日期:2004-07-01 00:00:00

  • Management of fertility in patients treated for Hodgkin's lymphoma.

    abstract::The risk of developing premature ovarian failure and azoospermia is a major concern in long-term survivors treated for Hodgkin's lymphoma. Alkylating chemotherapy containing procarbazine and/or cyclophosphamide causes prolonged azoospermia in 90-100% of men and premature ovarian failure in 5-25% of women under the age...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:10.3324/haematol.2011.045856

    authors: Harel S,Fermé C,Poirot C

    更新日期:2011-11-01 00:00:00

  • Density gradient separation of hematopoietic stem cells in autologous bone marrow transplantation.

    abstract::Recently, the principles of density gradient cell separation have been transferred to the marrow fractionation, and the Ficoll technique by using a COBE 2991 blood cell processor has been developed and widely employed as well. This method is particularly useful in view of a chemical antineoplastic purging intended for...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:

    authors: Iacone A,Quaglietta AM,D'Antonio D,Accorsi P,Dragani A,Angrilli F,Berardi A,Angelini A,Di Bartolomeo P,Di Bartolomeo G

    更新日期:1991-03-01 00:00:00

  • Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease.

    abstract:BACKGROUND:Chronic graft-versus-host disease is a common late complication of allogeneic hematopoietic stem cell transplantation. Corticosteroids are the standard initial treatment. Second-line treatment has not been well defined. We evaluated the effectiveness and safety of low doses of alemtuzumab plus low doses of r...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.054577

    authors: Gutiérrez-Aguirre CH,Cantú-Rodríguez OG,Borjas-Almaguer OD,González-Llano O,Jaime-Pérez JC,Solano-Genesta M,Gómez-Guijosa M,Mancias-Guerra C,Tarin L,Gómez-Almaguer D

    更新日期:2012-05-01 00:00:00

  • Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis.

    abstract:BACKGROUND:Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studie...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.3324/haematol.2011.042937

    authors: Volejnikova J,Mejstrikova E,Valova T,Reznickova L,Hodonska L,Mihal V,Sterba J,Jabali Y,Prochazkova D,Blazek B,Hak J,Cerna Z,Hrusak O,Stary J,Trka J,Fronkova E

    更新日期:2011-12-01 00:00:00

  • CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes.

    abstract::CLLU1, located at chromosome 12q22, encodes a transcript specific to chronic lymphocytic leukemia and has potential prognostic value. We assessed the value of CLLU1 expression in the LRF CLL4 randomized trial. Samples from 515 patients with chronic lymphocytic leukemia were collected immediately before the start of tr...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2012.070201

    authors: Gonzalez D,Else M,Wren D,Usai M,Buhl AM,Parker A,Oscier D,Morgan G,Catovsky D

    更新日期:2013-02-01 00:00:00

  • Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure.

    abstract::Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2012.066217

    authors: Seiki Y,Sasaki Y,Hosokawa K,Saito C,Sugimori N,Yamazaki H,Takami A,Nakao S

    更新日期:2013-06-01 00:00:00

  • Immunomodulatory drugs downregulate IKZF1 leading to expansion of hematopoietic progenitors with concomitant block of megakaryocytic maturation.

    abstract::The immunomodulatory drugs, lenalidomide and pomalidomide yield high response rates in multiple myeloma patients, but are associated with a high rate of thrombocytopenia and increased risk of secondary hematologic malignancies. Here, we demonstrate that the immunomodulatory drugs induce self-renewal of hematopoietic p...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2018.188227

    authors: Liu A,Li S,Donnenberg V,Fu J,Gollin SM,Ma H,Lu C,Stolz DB,Mapara MY,Monaghan SA,Lentzsch S

    更新日期:2018-10-01 00:00:00

  • Elongation factor 1 (EF1alpha) promoter in a lentiviral backbone improves expression of the CD20 suicide gene in primary T lymphocytes allowing efficient rituximab-mediated lysis.

    abstract:BACKGROUND AND OBJECTIVES:CD20 has been proposed as a novel suicide gene system for the treatment of graft-versus-host disease (GVHD), a fatal complication of allogeneic bone marrow transplantation: indeed expression of the human non-immunogenic exogenous CD20 protein allows positive immunoselection of transduced cells...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Serafini M,Bonamino M,Golay J,Introna M

    更新日期:2004-01-01 00:00:00

  • Hepatic and splenic mycosis in children with acute leukemia.

    abstract::Three cases of hepatic and/or splenic mycosis in children with acute leukemia are reported. Patients presented with fever not responding to broad spectrum antibiotics during or after prolonged and profound neutropenia. Noteworthy, in 1 case no abnormality in liver function tests was detectable at diagnosis. CT scan sh...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Moroni C,Castagnola E,Callea F,Lanino E,Rizzo A,Savioli C,Taccone A,Tomà P,Viscoli C

    更新日期:1991-07-01 00:00:00

  • A novel transgenic mouse model produced from lentiviral germline integration for the study of beta-thalassemia gene therapy.

    abstract:BACKGROUND:beta-thalassemia is one of the most common genetic diseases in the world and requires extensive therapy. Lentiviral-mediated gene therapy has been successfully exploited in the treatment of beta-thalassemia and showed promise in clinical application. Using a human beta-globin transgenic mouse line in a beta-...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.12010

    authors: Li W,Xie S,Guo X,Gong X,Wang S,Lin D,Zhang J,Ren Z,Huang S,Zeng F,Zeng Y

    更新日期:2008-03-01 00:00:00

  • 3q aberration and monosomy 7 in ANLL presenting with high platelet count and diabetes insipidus.

    abstract::Diabetes insipidus and thrombocytosis were presenting symptoms in a case of adult ANLL-M1. Cytogenetic investigations revealed a typical 3q rearrangement, i.e. inv(3)(q21q26). A subclone with monosomy 7 was also found and documented by FISH analysis. Correlations between clinical/hematological features and cytogenetic...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: La Starza R,Falzetti D,Fania C,Tabilio A,Martelli MF,Mecucci C

    更新日期:1994-07-01 00:00:00

  • Mitoxantrone, etoposide, cisplatin and dexamethasone (MEPD) as salvage chemotherapy in resistant non-Hodgkin's lymphoma.

    abstract:BACKGROUND:An effective second-line treatment for intermediate and high grade non-Hodgkin's lymphoma is greatly needed since 30% of patients do not achieved complete remission (CR) and another 20% to 30% of the CRs will eventually relapse. METHODS:A four-drug combination with Mitoxantrone, Etoposide, Cisplatin and Dex...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:

    authors: Vitolo U,Orsucci L,Bertini M,Cavallero G,Gallamini A,Ghio R,Levis A,Rota-Scalabrini D,Resegotti L

    更新日期:1991-01-01 00:00:00

  • Autologous blood stem cell transplantation for acute myeloblastic leukemia in first complete remission. Intensification therapy before transplantation does not prolong disease-free survival.

    abstract:BACKGROUND AND OBJECTIVE:To compare the clinical results of two consecutive therapeutic protocols including autologous blood stem cell transplantation (ABSCT) for patients with de novo acute myeloblastic leukemia (AML) in first complete remission (CR1). DESIGN AND METHODS:Between November 1989 and January 1997, 50 pat...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:

    authors: de la Rubia J,Sanz GF,Martín G,Martínez J,Cervera J,Solves P,Jiménez C,Arnao M,Vicente A,Jarque I,Sempere A,Sanz MA

    更新日期:1999-02-01 00:00:00

  • MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation.

    abstract::MicroRNA-34b down-regulation in acute myeloid leukemia was previously shown to induce CREB overexpression, thereby causing leukemia proliferation in vitro and in vivo. The role of microRNA-34b and CREB in patients with myeloid malignancies has never been evaluated. We examined microRNA-34b expression and the methylati...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2012.070664

    authors: Pigazzi M,Manara E,Bresolin S,Tregnago C,Beghin A,Baron E,Giarin E,Cho EC,Masetti R,Rao DS,Sakamoto KM,Basso G

    更新日期:2013-04-01 00:00:00

  • Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France.

    abstract::Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2013.092254

    authors: Labopin M,Ruggeri A,Gorin NC,Gluckman E,Blaise D,Mannone L,Milpied N,Yakoub-Agha I,Deconinck E,Michallet M,Fegueux N,Socié G,Nguyen S,Cahn JY,de Revel T,Garnier F,Faucher C,Taright N,Kenzey C,Volt F,Bertrand D,M

    更新日期:2014-03-01 00:00:00

  • Immunophenotypic characterization of reactive and neoplastic plasmacytoid dendritic cells permits establishment of a 10-color flow cytometric panel for initial workup and residual disease evaluation of blastic plasmacytoid dendritic cell neoplasm.

    abstract::Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic neoplasm whose immunophenotype remains incompletely characterized, particularly in terms of distinction from reactive plasmacytoid dendritic cells (PDCs). This limitation complicates detection of low-level involvement by BPDCN as well as mini...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2020.247569

    authors: Wang W,Khoury JD,Miranda RN,Jorgensen JL,Xu J,Loghavi S,Li S,Pemmaraju N,Nguyen T,Medeiros LJ,Wang SA

    更新日期:2020-04-02 00:00:00

  • Seminested polymerase chain reaction and heteroduplex analysis detects the monoclonality of IgH rearrangement in follicular lymphoma patients with high sensitivity.

    abstract::A new method, combining seminested polymerase chain reaction (PCR) with heteroduplex analysis, was utilized to detect follicular lymphoma (FL) cells in peripheral blood. The method, based on the detection of IgH rearrangements in DNA, detected the presence of monoclonal B cells in FL patients with a high frequency. ...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Oehadian A,Koide N,Mu MM,Hassan F,Yoshida T,Yokochi T

    更新日期:2005-02-01 00:00:00