Amelioration of Sardinian beta0 thalassemia by genetic modifiers.

Abstract:

:Sardinian beta-thalassemia patients all are homozygotes for the same null allele in the beta-globin gene, but the clinical manifestations are extremely variable in severity. Previous studies have shown that the coinheritance of alpha-thalassemia or the presence of genetic variants that sustain fetal hemoglobin production has a strong impact on ameliorating the clinical phenotype. Here we evaluate the contribution of variants in the BCL11A, and HBS1L-MYB genes, implicated in the regulation of fetal hemoglobin, and of alpha-thalassemia coinheritance in 50 thalassemia intermedia and 75 thalassemia major patients. We confirm that alpha-thalassemia and allele C of single nucleotide polymorphism rs-11886868 in BCL11A were selectively represented in thalassemia intermedia patients. Moreover, allele G at single nucleotide polymorphism rs9389268 in the HBS1L-MYB locus was significantly more frequent in the thalassemia intermedia patients. This trio of genetic factors can account for 75% of the variation differences in phenotype severity.

journal_name

Blood

journal_title

Blood

authors

Galanello R,Sanna S,Perseu L,Sollaino MC,Satta S,Lai ME,Barella S,Uda M,Usala G,Abecasis GR,Cao A

doi

10.1182/blood-2009-04-217901

subject

Has Abstract

pub_date

2009-10-29 00:00:00

pages

3935-7

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2009-04-217901

journal_volume

114

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA.

    abstract::Current immunotherapeutic trials for patients with multiple myeloma (MM) focus on the idiotype (Id) as a tumor-specific antigen for active immunization. To bypass the need for the identification of shared MM-associated antigens and the characterization of possible immunogenic T-cell epitopes in a human leukocyte antig...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-04-1273

    authors: Milazzo C,Reichardt VL,Müller MR,Grünebach F,Brossart P

    更新日期:2003-02-01 00:00:00

  • A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation.

    abstract::Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases. Disease resistance can occur if donor T cells are not appropriately activated in vivo. Ex vivo T-ce...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-08-3373

    authors: Porter DL,Levine BL,Bunin N,Stadtmauer EA,Luger SM,Goldstein S,Loren A,Phillips J,Nasta S,Perl A,Schuster S,Tsai D,Sohal A,Veloso E,Emerson S,June CH

    更新日期:2006-02-15 00:00:00

  • Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma.

    abstract::Interleukin-15 (IL-15) induces proliferation and promotes cell survival of human T and B lymphocytes, natural killer cells, and neutrophils. Here we report the constitutive expression of a functional IL-15 receptor (IL-15R) in 6 of 6 myeloma cell lines and in CD38(high)/CD45(low )plasma cells belonging to 14 of 14 pat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tinhofer I,Marschitz I,Henn T,Egle A,Greil R

    更新日期:2000-01-15 00:00:00

  • A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma.

    abstract::We report results from a study exploring the combination of romidepsin, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma (MM) previously treated with > 1 prior therapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combination using a novel accelerated ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-03-339879

    authors: Harrison SJ,Quach H,Link E,Seymour JF,Ritchie DS,Ruell S,Dean J,Januszewicz H,Johnstone R,Neeson P,Dickinson M,Nichols J,Prince HM

    更新日期:2011-12-08 00:00:00

  • Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript.

    abstract::In the majority of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) patients, the c-abl gene is fused to the bcr gene, resulting in the transcription of an 8.5 kb chimeric bcr-abl mRNA, which is translated into a p210bcr-abl fusion protein. In about 50% of the Ph-positive acute lymphoid leukemias (ALL), the b...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Selleri L,von Lindern M,Hermans A,Meijer D,Torelli G,Grosveld G

    更新日期:1990-03-01 00:00:00

  • Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation.

    abstract::Cellular oxygen partial pressure is sensed by a family of prolyl-4-hydroxylase domain (PHD) enzymes that modify hypoxia-inducible factor (HIF)alpha subunits. Upon hydroxylation under normoxic conditions, HIFalpha is bound by the von Hippel-Lindau tumor suppressor protein and targeted for proteasomal destruction. Since...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-10-3980

    authors: Martin F,Linden T,Katschinski DM,Oehme F,Flamme I,Mukhopadhyay CK,Eckhardt K,Tröger J,Barth S,Camenisch G,Wenger RH

    更新日期:2005-06-15 00:00:00

  • Familial and congenital polycythemia in three unrelated families.

    abstract::Three families with polycythemia inherited through apparently different modes are described. Secondary causes of polycythemia were ruled out. Erythropoietin (EPO) levels were normal or low, even after phlebotomy. In vitro erythroid colony growth in standard assay cultures containing EPO was normal; however, in the abs...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Emanuel PD,Eaves CJ,Broudy VC,Papayannopoulou T,Moore MR,D'Andrea AD,Prchal JF,Eaves AC,Prchal JT

    更新日期:1992-06-01 00:00:00

  • Anemia in children with cancer is associated with decreased erythropoietic activity and not with inadequate erythropoietin production.

    abstract::A defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect, anemic cancer patients, both adults and children, have been treated with recombinant human EPO (rHuEPO). To furth...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Corazza F,Beguin Y,Bergmann P,André M,Ferster A,Devalck C,Fondu P,Buyse M,Sariban E

    更新日期:1998-09-01 00:00:00

  • G-protein-gated inwardly rectifying potassium channels regulate ADP-induced cPLA2 activity in platelets through Src family kinases.

    abstract::ADP-induced TXA2 generation requires the costimulation of P2Y1, P2Y12, and the GPIIb/IIIa receptors. Signaling events downstream of the P2Y receptors that contribute to ADP-induced TXA2 generation have not been clearly delineated. In this study, we have investigated the role of G-protein-gated inwardly rectifying pota...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-03-010330

    authors: Shankar H,Kahner BN,Prabhakar J,Lakhani P,Kim S,Kunapuli SP

    更新日期:2006-11-01 00:00:00

  • Fbw7γ-mediated degradation of KLF13 prevents RANTES expression in resting human but not murine T lymphocytes.

    abstract::RANTES (CCL5) is a chemokine implicated in many human diseases. We previously showed that the transcription factor Kruppel-like factor 13 (KLF13) controls the late (3-5 days after activation) expression of RANTES in T lymphocytes and that KLF13 itself is translationally regulated through the 5'-untranslated region of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-03-415968

    authors: Kim DS,Zhang W,Millman SE,Hwang BJ,Kwon SJ,Clayberger C,Pagano M,Krensky AM

    更新日期:2012-08-23 00:00:00

  • CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma.

    abstract::Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-01-481713

    authors: Bhatt S,Ashlock BM,Natkunam Y,Sujoy V,Chapman JR,Ramos JC,Mesri EA,Lossos IS

    更新日期:2013-08-15 00:00:00

  • Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation.

    abstract::Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferatio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miller BA,Cheung JY,Tillotson DL,Hope SM,Scaduto RC Jr

    更新日期:1989-04-01 00:00:00

  • Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output.

    abstract::The granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3/IL-5 receptor family regulates the production and function of myeloid cells. These cytokines signal through receptor complexes that consist of unique ligand-binding alpha-chains and common signaling beta-chains. IL-5 is distinct from IL-3...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-03-208850

    authors: Beekman JM,Verhagen LP,Geijsen N,Coffer PJ

    更新日期:2009-10-29 00:00:00

  • Contribution of natural killer cells to inhibition of angiogenesis by interleukin-12.

    abstract::Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induce...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yao L,Sgadari C,Furuke K,Bloom ET,Teruya-Feldstein J,Tosato G

    更新日期:1999-03-01 00:00:00

  • Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells.

    abstract::The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3(+) (CD141(+)) subset DCs may be particularly effective in DC vaccination trials. BDCA-3(+) DCs ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-06-434498

    authors: Flinsenberg TW,Compeer EB,Koning D,Klein M,Amelung FJ,van Baarle D,Boelens JJ,Boes M

    更新日期:2012-12-20 00:00:00

  • Stimulation of murine colony-forming cells with high proliferative potential by the combination of GM-CSF and CSF-1.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages to act as an erythroid burst-promoting activity and to stimulate limited replication of spleen colony-forming cells. Here we demonstrate that murine GM-CSF alone or in co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McNiece IK,Robinson BE,Quesenberry PJ

    更新日期:1988-07-01 00:00:00

  • Potential and distribution of transplanted hematopoietic stem cells in a nonablated mouse model.

    abstract::Increasingly, allogeneic and even more often autologous bone marrow transplants are being done to correct a wide variety of diseases. In addition, autologous marrow transplants potentially provide an opportune means of delivering genes in transfected, engrafting stem cells. However, despite its widespread clinical use...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nilsson SK,Dooner MS,Tiarks CY,Weier HU,Quesenberry PJ

    更新日期:1997-06-01 00:00:00

  • Platelet modulation of polymorphonuclear leukocyte shear induced aggregation.

    abstract::A cone and plate viscometer and Coulter Counter were used to study platelet modulation of polymorphonuclear leukocyte (PMNL) aggregation caused by controlled shear stress. As an index of aggregation, the large-particle percentage (LPP) was calculated. This represents the ratio of aggregated cell count to total cell co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rhee BG,Hall ER,McIntire LV

    更新日期:1986-01-01 00:00:00

  • Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans.

    abstract::Recently various genetic defects in immunity mediated by interferon gamma (IFN-gamma) have been described, including mutations in the IFN-gamma receptor 1 (IFN-gammaR1) and receptor 2 (IFN-gammaR2), signal transducer and activator of transcription 1 (STAT 1), and interleukin 12 receptor beta 1 (IL-12Rbeta1), and IL-12...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-04-1065

    authors: Höflich C,Sabat R,Rosseau S,Temmesfeld B,Slevogt H,Döcke WD,Grütz G,Meisel C,Halle E,Göbel UB,Volk HD,Suttorp N

    更新日期:2004-01-15 00:00:00

  • Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies.

    abstract::CD20 is a nonglycosylated 33 to 37 kD phosphoprotein involved in B-cell signaling that subserves important functions in the regulation of B-cell proliferation and differentiation. In addition, this B-cell surface antigen has been shown recently to be an effective target for immunotherapy of B-cell malignancies using c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Shan D,Ledbetter JA,Press OW

    更新日期:1998-03-01 00:00:00

  • Evidence that calpains and elastase do not produce the von Willebrand factor fragments present in normal plasma and IIA von Willebrand disease.

    abstract::Recent evidence suggests that proteolysis plays an important role in some forms of inherited and acquired von Willebrand disease (vWD). Because calpains and one or more enzymes released from polymorphonuclear leukocytes are known to proteolyze von Willebrand factor (vWF) in vitro with resultant loss of large multimers...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Berkowitz SD,Nozaki H,Titani K,Murachi T,Plow EF,Zimmerman TS

    更新日期:1988-08-01 00:00:00

  • Antithymocyte globulin has limited efficacy and substantial toxicity in unselected anemic patients with myelodysplastic syndrome.

    abstract::Antithymocyte globulin (ATG) has recently been popularized as an effective treatment in myelodysplastic syndrome (MDS). We treated 8 anemic MDS patients (refractory anemia [RA] and refractory anemia with excess blasts [RAEB-1]) with ATG (40 mg/kg/d for 4 days) and prednisone in a phase 2 trial. The study was stopped e...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2002-09-2867

    authors: Steensma DP,Dispenzieri A,Moore SB,Schroeder G,Tefferi A

    更新日期:2003-03-15 00:00:00

  • Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents.

    abstract::A technique has been developed for handling human bone marrow cells intended for the examination of DNA repair synthesis. DNA-repair synthesis, induced by melphalan and nitrogen mustard, was measured as the incorporation of 3H-thymidine, registered by autoradiography as unscheduled DNA synthesis (UDS). Comparison of v...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lewensohn R,Ringborg U

    更新日期:1979-12-01 00:00:00

  • Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion.

    abstract::Secretion of platelet granules is necessary for normal hemostasis. Platelet secretion requires soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex formation between different members of the syntaxin, SNAP-25, and vesicle-associated membrane protein (VAMP) gene families. Using m...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v100.3.1081

    authors: Polgár J,Chung SH,Reed GL

    更新日期:2002-08-01 00:00:00

  • Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma.

    abstract::During the course of multiple myeloma (MM), new monoclonal proteins of an isotype distinct from the original clone, referred to as secondary monoclonal gammopathy of undetermined significance (MGUS), have been described. We report on the frequency, characteristics, and outcome of secondary MGUS. Of the 1942 patients w...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-04-349175

    authors: Wadhera RK,Kyle RA,Larson DR,Dispenzieri A,Kumar S,Lazarus HM,Rajkumar SV

    更新日期:2011-09-15 00:00:00

  • Modulation of the apoptotic response of human myeloid leukemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein.

    abstract::It has previously been shown that human granulocyte-macrophage colony-stimulating factor (GM-CSF) can be fused to a truncated diphtheria toxin (DT) to produce a recombinant fusion toxin that kills GM-CSF receptor-bearing cells. We now report that DT388-GM-CSF induces apoptosis and inhibition of colony formation in sem...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Frankel AE,Hall PD,Burbage C,Vesely J,Willingham M,Bhalla K,Kreitman RJ

    更新日期:1997-11-01 00:00:00

  • A ligand-receptor signaling threshold model of stem cell differentiation control: a biologically conserved mechanism applicable to hematopoiesis.

    abstract::A major limitation to the widespread use of hematopoietic stem cells (HSC) is the relatively crude level of our knowledge of how to maintain these cells in vitro without loss of the long-term multilineage growth and differentiation properties required for their clinical utility. An experimental and theoretical framewo...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:

    authors: Zandstra PW,Lauffenburger DA,Eaves CJ

    更新日期:2000-08-15 00:00:00

  • Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans.

    abstract::Vascular calcification is a marker of increased cardiovascular risk. Vitamin K-dependent matrix Gla protein (MGP) is important in inhibiting calcification. Because MGP activation is vitamin K dependent, we performed a cross-sectional study investigating the relationship between the use of vitamin K antagonists and ext...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-01-264598

    authors: Rennenberg RJ,van Varik BJ,Schurgers LJ,Hamulyak K,Ten Cate H,Leiner T,Vermeer C,de Leeuw PW,Kroon AA

    更新日期:2010-06-17 00:00:00

  • The human leukocyte integrin CD11a promoter directs expression in leukocytes of transgenic mice.

    abstract::The human CD11a molecule is expressed specifically on lymphocytes, monocyte/macrophages, and neutrophils, in which it mediates important adhesion-related functions. We used 1.7 kb of regulatory sequences upstream from the human CD11a gene transcription start site to drive expression of a modified human CD4 reporter ge...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ritchie KA,Aprikian A,Gollahon KA,Hickstein DD

    更新日期:1995-07-01 00:00:00

  • Signaling through CD43 induces natural killer cell activation, chemokine release, and PYK-2 activation.

    abstract::Natural killer (NK) cell activation is the result of a balance between positive and negative signals triggered by specific membrane receptors. We report here the activation of NK cells induced through the transmembrane glycoprotein CD43 (leukosialin, sialophorin). Engagement of CD43 by specific antibodies stimulated t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nieto M,Rodríguez-Fernández JL,Navarro F,Sancho D,Frade JM,Mellado M,Martínez-A C,Cabañas C,Sánchez-Madrid F

    更新日期:1999-10-15 00:00:00