Mild iron deficiency does not ameliorate the phenotype of a murine erythropoietic protoporphyria model.

Abstract:

:Reduced ferrochelatase activity in erythropoietic protoporphyria (EPP) causes the accumulation of protoporphyrin IX (PPIX) leading to acute cutaneous photosensitivity and liver injury. Many EPP patients also have a mild hypochromic, microcytic anemia and iron deficiency. Iron deficiency can lead to decreased PPIX accumulation in another erythropoietic porphyria, congenital erythropoietic porphyria (CEP). Expression of the iron regulatory peptide hepcidin is negatively regulated by the serine protease TMPRSS6. Hepcidin induction by siRNA-mediated inhibition of TMPRSS6 expression reduces iron availability and induces iron deficiency. To interrogate the therapeutic potential of iron deficiency to modify EPP, we treated an ethylnitrosourea-induced mouse model of EPP, Fech m1Pas , with a GalNAc-conjugated Tmprss6 siRNA and PPIX levels, anemia and iron parameters were monitored. The GalNAc-RNAi therapeutic reduces Tmprss6 expression and induces mild iron deficiency in Fech m1Pas animals. However, decreases in erythrocyte PPIX levels and liver PPIX accumulation were not seen. These results indicate short-term induction of iron deficiency, at least in a murine model of EPP, does not lead to decreased PPIX production.

journal_name

Am J Hematol

authors

Schmidt PJ,Hollowell ML,Fitzgerald K,Butler JS,Fleming MD

doi

10.1002/ajh.25743

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

492-496

issue

5

eissn

0361-8609

issn

1096-8652

journal_volume

95

pub_type

杂志文章
  • Which steroids should we choose for the treatment of adult acute lymphoblastic leukemia?

    abstract::Corticosteroids are essential and one of the mainstays in the treatment of acute lymphoblastic leukemia (ALL). In vitro assays show that dexamethasone(DXM) is five to six times more cytotoxic to leukemic lymphoblasts than prednisolone (PDN) [1], and the use of DXM as an alternative drug for PDN is an important issue i...

    journal_title:American journal of hematology

    pub_type: 信件,随机对照试验

    doi:10.1002/ajh.21827

    authors: Zheng C,Liu X,Wu J,Cai X,Zhu W,Sun Z

    更新日期:2010-10-01 00:00:00

  • Disturbance of plasma and platelet thrombospondin levels in sickle cell disease.

    abstract::Thrombospondin (TSP), a large protein found in platelet alpha-granules (as TSP-1), mediates adhesion of sickle reticulocytes to cultured vascular endothelium. To further explore the physiologic relevance of this observation, we have measured plasma TSP levels and platelet TSP-1 content in subjects with sickle cell dis...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1096-8652(199604)51:4<296::AID-AJH8>

    authors: Browne PV,Mosher DF,Steinberg MH,Hebbel RP

    更新日期:1996-04-01 00:00:00

  • Acute myeloid leukemia: 2014 update on risk-stratification and management.

    abstract:OVERVIEW:Evidence suggests that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment r...

    journal_title:American journal of hematology

    pub_type: 杂志文章,评审

    doi:10.1002/ajh.23834

    authors: Estey EH

    更新日期:2014-11-01 00:00:00

  • Hodgkin disease in a patient with common variable immunodeficiency.

    abstract::Extensive extralymphatic Hodgkin disease developed in a young man with common variable immunodeficiency manifested by hypogammaglobulinemia, recurrent sinopulmonary infections, and multiple autoimmune phenomena. Both humoral and cell-mediated immune dysfunction were present prior to treatment. After two cycles of chem...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830320212

    authors: Fesus SM,Hagemeister FB,Manning J

    更新日期:1989-10-01 00:00:00

  • Fetal hemoglobin expression in compound heterozygotes for -117 (G-->A)A gamma HPFH and beta zero 39 nonsense thalassemia.

    abstract::The -117(G-->A)A gamma hereditary persistence of fetal hemoglobin (Greek HPFH) and beta zero 39-thal mutations are rather frequent in Sardinia so that their interaction is to be expected. Characterization of eight compound heterozygotes for these defects indicated that HPFH was linked to haplotype VII and beta zero 39...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830490402

    authors: Pistidda P,Frogheri L,Oggiano L,Guiso L,Manca L,Dore F,Masala B,Gilman JG,Longinotti M

    更新日期:1995-08-01 00:00:00

  • On the value of menorrhagia as a predictor for coagulation disorders.

    abstract::The value of menorrhagia as a predictor for mild bleeding disorders has been very little studied and the results are divergent. In the present study on 30 women with objectively verified menorrhagia, we found a significantly increased prevalence of von Willebrand's disease (20%). By keeping a strict sampling and labor...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1096-8652(199612)53:4<234::AID-AJH4>

    authors: Edlund M,Blombäck M,von Schoultz B,Andersson O

    更新日期:1996-12-01 00:00:00

  • Late appearance of the Philadelphia chromosome with monosomy 7 in a patient with de novo AML with trilineage myelodysplasia.

    abstract::We report here a patient with de novo acute myelocytic leukemia with trilineage myelodysplasia (AML/TMDS) in whom cytogenetic analysis was normal at diagnosis and in whom Philadelphia chromosome (Ph1) with monosomy 7 emerged at the terminal stage of the disease. Reverse transcription polymerse chain reaction (RT-PCTR)...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830490413

    authors: Matsue K,Miyamoto T,Ito M,Tsukuda K

    更新日期:1995-08-01 00:00:00

  • The prognostic value of monosomal karyotype (MK) in higher-risk patients with myelodysplastic syndromes treated with 5-Azacitidine: A retrospective analysis of the Hellenic (Greek) Myelodysplastic syndromes Study Group.

    abstract::In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk Myelodysplastic Syndromes (MDS) patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytoge...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.25111

    authors: Papageorgiou SG,Vasilatou D,Kontos CK,Kotsianidis I,Symeonidis A,Galanopoulos AG,Hatzimichael E,Megalakaki A,Poulakidas E,Diamantopoulos P,Vassilakopoulos TP,Zikos P,Papadaki H,Mparmparousi D,Bouronikou E,Panayiotidis P,V

    更新日期:2018-07-01 00:00:00

  • High-density lipoprotein fails to inhibit serotonin-induced activation of blood platelets.

    abstract::High-density lipoprotein (HDL) of 100-400 micrograms/ml did not prevent morphological alterations of human blood platelets treated with serotonin (1-5 microM). Highly concentrated HDL (1,200 micrograms/ml) appeared to activate platelets in vitro. These findings indicate that whole HDL may not inhibit agonist-induced p...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830500417

    authors: Pfennig O,Zhao B,Frye S,Dierichs R

    更新日期:1995-12-01 00:00:00

  • Venous insufficiency is not the cause of leg ulcers in sickle cell disease.

    abstract::Leg ulcers are a well recognized complication of sickle cell disease that has been attributed to venous insufficiency. We studied 16 patients with sickle cell disease and active ulcers using venous pulse volume recordings and photoplethysmography (Doppler studies). Based on hemodynamic monitoring, all 16 patients exhi...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830370215

    authors: Billett HH,Patel Y,Rivers SP

    更新日期:1991-06-01 00:00:00

  • Comparative study of micro-transplantation from HLA fully mismatched unrelated and partly matched related donors in acute myeloid leukemia.

    abstract::Micro-transplantation (MST) by chemotherapy, combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antige...

    journal_title:American journal of hematology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1002/ajh.25780

    authors: Hu KX,Du X,Guo M,Yu CL,Qiao JH,Sun QY,Zuo HL,Cai B,Huang YJ,Ai HS,Dong Z,Wang Y

    更新日期:2020-06-01 00:00:00

  • Efficacy of the high molecular weight fraction of plasma for the maintenance of pregnancy associated with thrombotic thrombocytopenic purpura.

    abstract::We have investigated the methods for the maintenance of a pregnancy in a patient with thrombotic thrombocytopenic purpura (TTP), said condition, since 1984, having been controlled by a plasma infusion every 3 to 4 weeks. In a preliminary trial it was confirmed that an infusion of the high molecular weight fraction (HM...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830350307

    authors: Koyama T,Suehiro A,Kakishita E,Taira S,Isojima S,Norioka M,Ito K

    更新日期:1990-11-01 00:00:00

  • 2021 clinical trials update: Innovations in hemophilia therapy.

    abstract::Therapies engineered to prolong clotting factor protein circulation time, manipulate the balance of pro-coagulant and anti-coagulant proteins, or introduce new genetic material to enable endogenous factor protein production dominate the clinical trial landscape of hemophilia. The availability of clotting factor concen...

    journal_title:American journal of hematology

    pub_type: 杂志文章,评审

    doi:10.1002/ajh.26018

    authors: Croteau SE,Wang M,Wheeler AP

    更新日期:2021-01-01 00:00:00

  • Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy.

    abstract::We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one pati...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1096-8652(199608)52:4<310::AID-AJH11

    authors: Mach-Pascual S,Samii K,Beris P

    更新日期:1996-08-01 00:00:00

  • Some studies with a monoclonal antibody directed against human fibrinogen.

    abstract::Some properties of a monoclonal antibody generated against the fibrinogen component of a factor VIII preparation were investigated. The antibody bound with equal affinity in solid phase radioimmunoassays to fibrinogens isolated from both normal patients and patients with von Willebrand disease. It reacted in a sensiti...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830180202

    authors: Francis SE,Joshua DE,Exner T,Kronenberg H

    更新日期:1985-02-01 00:00:00

  • Isolation and characterization of granulocyte lysosomal proteins and study of their effects on the clotting system.

    abstract::Lysosomes (granules) of rabbit PMN leukocytes were extracted with either HCl or H2SO4, and the extracts were chromatographed over Sephadex to separate protein constituents. Some of the low molecular weight cationic proteins homogeneous on SDS PAGE (8% and 12.5% gels) were characterized by electrophoretic mobility in a...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830070309

    authors: Herion JC,Bucher JR,Penniall R,Walker RI,Baker M,Roberts HR

    更新日期:1979-01-01 00:00:00

  • Low dose cytosine arabinoside in acute myeloid leukemia: remission is not due to differentiation induction.

    abstract::A patient with acute nonlymphoblastic leukemia (FAB M4), showing a near tetraploid chromosome complement on his marrow cells, was treated with low dose cytosine arabinoside and achieved remission. During remission the near tetraploid marrow chromosome complement disappeared and reappeared upon relapse of leukemia. The...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830190412

    authors: Pinkerton PH,London B,Cowan DH

    更新日期:1985-08-01 00:00:00

  • Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil kinetics and function in normal human volunteers.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 microg/m2) was administered subcutaneously to 7 normal volunteers for up to 14 days to study its effects on neutrophil kinetics and function. With treatment, blood neutrophil counts rose gradually to peak at 3 1/2 times baseline by day 14. At day 5 marrow ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199801)57:1<7::aid-ajh2>3.

    authors: Dale DC,Liles WC,Llewellyn C,Price TH

    更新日期:1998-01-01 00:00:00

  • Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma.

    abstract::We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we de...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.24223

    authors: Maurer MJ,Jais JP,Ghesquières H,Witzig TE,Hong F,Haioun C,Thompson CA,Thieblemont C,Micallef IN,Porrata LF,Ribrag V,Nowakowski GS,Casasnovas O,Bologna S,Morschhauser F,Morrison VA,Peterson BA,Macon WR,Copie-Bergman C

    更新日期:2016-02-01 00:00:00

  • IKAROS expression in distinct bone marrow cell populations as a candidate biomarker for outcome with lenalidomide-dexamethasone therapy in multiple myeloma.

    abstract::Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the po...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.24634

    authors: Bolomsky A,Hübl W,Spada S,Müldür E,Schlangen K,Heintel D,Rocci A,Weißmann A,Fritz V,Willheim M,Zojer N,Palumbo A,Ludwig H

    更新日期:2017-03-01 00:00:00

  • Characteristics of late transplant-associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation.

    abstract::Transplant-associated thrombotic microangiopathy (TA-TMA) has a wide range of presentations after hematopoietic stem-cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA-TMA. Among the 1451 HSCT recipients, early TA-TMA occurred ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.25922

    authors: Heybeli C,Sridharan M,Alkhateeb HB,Villasboas Bisneto JC,Buadi FK,Chen D,Dingli D,Dispenzieri A,Gertz MA,Go RS,Hashmi SK,Hayman SR,Hogan WJ,Inwards DJ,Kenderian SS,Kumar SK,Litzow MR,Porrata LF,Lacy MQ,Micallef IN,

    更新日期:2020-07-02 00:00:00

  • Myelodysplastic syndromes: 2015 Update on diagnosis, risk-stratification and management.

    abstract:DISEASE OVERVIEW:The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic th...

    journal_title:American journal of hematology

    pub_type: 杂志文章,评审

    doi:10.1002/ajh.24102

    authors: Garcia-Manero G

    更新日期:2015-09-01 00:00:00

  • Laparoscopic splenectomies for idiopathic thrombocytopenic purpura: experience of sixty cases.

    abstract::We performed a laparoscopic splenectomy (LS) in 60 patients (age 9-83, 45 females) with idiopathic thrombocytopenic purpura (ITP) who did not achieve sustained remission on steroid therapy. Using a modified procedure, the mean duration of LS was 78 min (range 25-240 min) and surgery was associated with only 5% major a...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(200001)63:1<7::aid-ajh2>3.

    authors: Szold A,Schwartz J,Abu-Abeid S,Bulvik S,Eldor A

    更新日期:2000-01-01 00:00:00

  • Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis.

    abstract::The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order to establish its value ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.23672

    authors: Kristensen T,Vestergaard H,Bindslev-Jensen C,Møller MB,Broesby-Olsen S,Mastocytosis Centre, Odense University Hospital (MastOUH).

    更新日期:2014-05-01 00:00:00

  • Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies.

    abstract::Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon but distinctive clinicoradiological entity comprising of headache, seizures, visual disturbance, and altered mental function, in association with posterior cerebral white matter edema. With appropriate management, RPLS is reversible in the majorit...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.20147

    authors: Tam CS,Galanos J,Seymour JF,Pitman AG,Stark RJ,Prince HM

    更新日期:2004-09-01 00:00:00

  • CD34 expression is associated with poor clinical outcome in patients with acute promyelocytic leukemia.

    abstract::This study investigated the clinical characteristics and prognostic relevance of CD34 expression in 47 patients with acute promyelocytic leukemia (APL), showing t(15;17) or PML/RARalpha. Ten (21.3%) of the APL patients were CD34(+). CD34 expression was associated with hypogranular morphology (P = 0.002) and hyperleuko...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.10337

    authors: Lee JJ,Cho D,Chung IJ,Cho SH,Park KS,Park MR,Ryang DW,Kim HJ

    更新日期:2003-07-01 00:00:00

  • Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease.

    abstract::Sickle cell disease (SCD) is associated with early mortality. We sought to determine the incidence, cause, and risk factors for death in an adult population of patients with SCD. All patients aged >/=18 years seen at the Adult Sickle Cell Center at Duke University Medical Center between January 2000 and April 2005 wer...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.21569

    authors: Fitzhugh CD,Lauder N,Jonassaint JC,Telen MJ,Zhao X,Wright EC,Gilliam FR,De Castro LM

    更新日期:2010-01-01 00:00:00

  • A multi-institutional comparison of mitoxantrone, etoposide, and cytarabine vs high-dose cytarabine and mitoxantrone therapy for patients with relapsed or refractory acute myeloid leukemia.

    abstract::Relapsed or refractory acute myeloid leukemia (R/R AML) has a poor prognosis and is best treated with salvage chemotherapy as a bridge to allogeneic stem cell transplant (alloSCT). However, the optimal salvage therapy remains unknown. Here we compared two salvage regimens; mitoxantrone, etoposide, and cytarabine (MEC)...

    journal_title:American journal of hematology

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ajh.25838

    authors: Christian S,Arain S,Patel P,Khan I,Calip GS,Agrawal V,Sweiss K,Griffin S,Cahill K,Konig H,Esen A,Shergill A,Odenike O,Stock W,Quigley JG

    更新日期:2020-08-01 00:00:00

  • Clinical manifestations of essential thrombocythemia in young adults.

    abstract::Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by isolated overproduction of platelets, thrombohemorrhagic complications, and a median age of 50-60. When it occurs in younger patients, the incidence of complications has been reported to be quite low, with a good long-term prognosis. We r...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830330106

    authors: Millard FE,Hunter CS,Anderson M,Edelman MJ,Kosty MP,Luiken GA,Marino GG

    更新日期:1990-01-01 00:00:00

  • Transgenic mouse model of pharmacologic induction of fetal hemoglobin: studies using a new ribonucleotide reductase inhibitor, Didox.

    abstract::Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has been done mainly in baboons and macaques. We investigated whether results in transgenic mice can predict the stimulation of fetal hemoglobin in primates, by testing gamma globin induction in response to a new ribonucleotide reductase inh...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830450208

    authors: Pace BS,Elford HL,Stamatoyannopoulos G

    更新日期:1994-02-01 00:00:00