Mutant calreticulin-expressing cells induce monocyte hyperreactivity through a paracrine mechanism.

Abstract:

:Mutations in the calreticulin gene (CALR) were recently identified in approximately 70-80% of patients with JAK2-V617F-negative essential thrombocytosis and primary myelofibrosis. All frameshift mutations generate a recurring novel C-terminus. Here we provide evidence that mutant calreticulin does not accumulate efficiently in cells and is abnormally enriched in the nucleus and extracellular space compared to wildtype calreticulin. The main determinant of these findings is the loss of the calcium-binding and KDEL domains. Expression of type I mutant CALR in Ba/F3 cells confers minimal IL-3-independent growth. Interestingly, expression of type I and type II mutant CALR in a nonhematopoietic cell line does not directly activate JAK/STAT signaling compared to wildtype CALR and JAK2-V617F expression. These results led us to investigate paracrine mechanisms of JAK/STAT activation. Here we show that conditioned media from cells expressing type I mutant CALR exaggerate cytokine production from normal monocytes with or without treatment with a toll-like receptor agonist. These effects are not dependent on the novel C-terminus. These studies offer novel insights into the mechanism of JAK/STAT activation in patients with JAK2-V617F-negative essential thrombocytosis and primary myelofibrosis.

journal_name

Am J Hematol

authors

Garbati MR,Welgan CA,Landefeld SH,Newell LF,Agarwal A,Dunlap JB,Chourasia TK,Lee H,Elferich J,Traer E,Rattray R,Cascio MJ,Press RD,Bagby GC,Tyner JW,Druker BJ,Dao KH

doi

10.1002/ajh.24245

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

211-9

issue

2

eissn

0361-8609

issn

1096-8652

journal_volume

91

pub_type

杂志文章
  • High prevalence of thrombocytopenia in SLE patients with a high level of anticardiolipin antibodies combined with lupus anticoagulant.

    abstract::The relationship between thrombocytopenia and the level of anticardiolipin antibodies (aCL) and/or the existence of lupus anticoagulant (LA) ware studied in 146 patients with systemic lupus erythematosus (SLE). These patients were divided into six groups: A, those LA positive with a high level of aCL (>10 U/ml) (10 ca...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199805)58:1<55::aid-ajh10>

    authors: Nojima J,Suehisa E,Kuratsune H,Machii T,Toku M,Tada H,Yamaguti K,Koike T,Kanakura Y,Kitani T,Amino N

    更新日期:1998-05-01 00:00:00

  • Circumstances of death in adult sickle cell disease patients.

    abstract::The purpose of the study was to analyze clinical and/or autopsy findings at the time of death among adults with sickle cell disease (SCD) at Howard University in Washington, DC over a 25-year period. A single physician recorded circumstances of death among 141 adult SCD patients he treated and knew well from 1976 to 2...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.20685

    authors: Darbari DS,Kple-Faget P,Kwagyan J,Rana S,Gordeuk VR,Castro O

    更新日期:2006-11-01 00:00:00

  • Prenatal and molecular diagnosis of hemophilia B.

    abstract::Prenatal diagnosis was carried out on a woman who had previously given birth to a son with a spontaneous mutation of C-->T transition at nt 31133 of the factor IX (F.IX) gene. The diagnosis was performed on chorionic villi sampling by the method of amplification-created restriction site (ACRS). It revealed a female fe...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1096-8652(199608)52:4<243::AID-AJH1>

    authors: Young JH,Wang JC,Gau JP,Hu HT

    更新日期:1996-08-01 00:00:00

  • Radiotherapy to control CNS lymphomatoid granulomatosis: a case report and review of the literature.

    abstract::Lymphomatoid granulomatosis (LG) is an uncommon but potentially fatal disease. The disease primarily involves the lungs; however, skin, renal, and central nervous system (CNS) are seen in varying proportions. Neurological involvement occurs in one third of the patients, and confers a worse prognosis. The use of radiot...

    journal_title:American journal of hematology

    pub_type: 杂志文章,评审

    doi:10.1002/(sici)1096-8652(199912)62:4<239::aid-ajh7>

    authors: Petrella TM,Walker IR,Jones GW,Leber B

    更新日期:1999-12-01 00:00:00

  • Variation in DNA content of immature normal bone marrow cells.

    abstract::A variability in DNA content detected was found with image cytometry, in immature bone marrow cells from 13 healthy donors (median age 31 yr). The mean coefficient of variation (C.V.) of the DNA content was found to be significantly (P = 0.0002) higher in immature blasts and promyelocytes than in mature granulocytes, ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830430412

    authors: Widell S,Auer G,Hast R,Reizenstein P

    更新日期:1993-08-01 00:00:00

  • World Health Organization-defined classification of myeloproliferative neoplasms: morphological reproducibility and clinical correlations--the Danish experience.

    abstract::We examined inter- and intraobserver reproducibility and concordance between histological diagnosis and independently collected clinical findings in a large series of patients with the major subtypes of myeloproliferative neoplasms (MPNs) and controls. Seven hematopathologists reviewed 272 bone marrow biopsies includi...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.23554

    authors: Madelung AB,Bondo H,Stamp I,Loevgreen P,Nielsen SL,Falensteen A,Knudsen H,Ehinger M,Dahl-Sørensen R,Mortensen NB,Svendsen KD,Lange T,Ralfkiaer E,Nielsen K,Hasselbalch HC,Thiele J

    更新日期:2013-12-01 00:00:00

  • Telomere length in myelodysplastic syndromes.

    abstract::We have studied telomere length in the bone marrow cells or the granulocyte and lymphocyte cell fractions of 54 patients with myelodysplastic syndromes (MDS) by Southern blot hybridization using the (TTAGGG)4 probe. The average telomere length expressed as the peak telomere repeat array (TRA) in the peripheral blood, ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199712)56:4<266::aid-ajh12

    authors: Boultwood J,Fidler C,Kusec R,Rack K,Elliott PJ,Atoyebi O,Chapman R,Oscier DG,Wainscoat JS

    更新日期:1997-12-01 00:00:00

  • AL amyloidosis associated with B-cell lymphoproliferative disorders: frequency and treatment outcomes.

    abstract::AL amyloidosis, a systemic disorder characterized by widespread deposition of amyloid fibrils derived from monoclonal Ig light chains in organs and soft tissues, is typically caused by an underlying plasma cell dyscrasia. However, this disease can also be associated rarely with a B-cell lymphoproliferative disorder. I...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.20635

    authors: Sanchorawala V,Blanchard E,Seldin DC,O'Hara C,Skinner M,Wright DG

    更新日期:2006-09-01 00:00:00

  • A single-center experience in 20 patients with infantile malignant osteopetrosis.

    abstract::Infantile malignant osteopetrosis (IMO) includes various genetic disorders that affect osteoclast development and/or function. Genotype-phenotype correlation studies in IMO have been hampered by the rarity and heterogeneity of the disease and by the severity of the clinical course, which often leads to death early in ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.21447

    authors: Mazzolari E,Forino C,Razza A,Porta F,Villa A,Notarangelo LD

    更新日期:2009-08-01 00:00:00

  • Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients.

    abstract::Although infectious complications represent a relevant cause of morbidity and mortality in patients with myelofibrosis (MF), little is known about their incidence, outcome and risk factors. We retrospectively evaluated a cohort of 507 MF patients, diagnosed between 1980 and 2014 in five Italian hematology centers, to ...

    journal_title:American journal of hematology

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ajh.24572

    authors: Polverelli N,Breccia M,Benevolo G,Martino B,Tieghi A,Latagliata R,Sabattini E,Riminucci M,Godio L,Catani L,Nicolosi M,Perricone M,Sollazzo D,Colafigli G,Campana A,Merli F,Vitolo U,Alimena G,Martinelli G,Lewis RE,V

    更新日期:2017-01-01 00:00:00

  • Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher-risk myelodysplastic syndromes.

    abstract::Lenalidomide and azacitidine are active in MDS patients, and may complement each other by targeting the bone marrow microenvironment and the malignant clone. A recent Phase I trial testing the lenalidomide and azacitidine combination yielded encouraging results; however, lenalidomide’s contribution was unclear. In thi...

    journal_title:American journal of hematology

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ajh.21891

    authors: Sekeres MA,O'Keefe C,List AF,Paulic K,Afable M 2nd,Englehaupt R,Maciejewski JP

    更新日期:2011-01-01 00:00:00

  • Retinoblastoma-related geneRb2/p130 are rarely mutated in Burkitt's lymphoma from Brazil.

    abstract::It has been suggested that alterations of cell cycle genes probably contribute to the pathogenesis of endemic Burkitt's lymphoma (BL) in addition to c-MYC translocation. Mutations disrupting the normal nuclear localization signal of the retinoblastoma-related gene Rb2/p130 have been documented in BL cell lines and pri...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.20749

    authors: Klumb CE,Magluta EP,Rezende LM,Apa AG,Alonso JF,Maia RC

    更新日期:2007-03-01 00:00:00

  • Enhancement of sickle erythrocyte adherence to endothelium by autologous platelets.

    abstract::The increased adhesiveness of sickle erythrocytes (SS RBC) to endothelial cells has been confirmed in a static system utilizing fresh umbilical vein endothelium. Adherence of SS RBC to the endothelium was as great in the presence of calcium-containing buffer as when incubated in plasma. SS RBC suspended in autologous ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830340110

    authors: Antonucci R,Walker R,Herion J,Orringer E

    更新日期:1990-05-01 00:00:00

  • Acute renal failure after intravenous anti-D immune globulin in an adult with immune thrombocytopenic purpura.

    abstract::Intravenous anti-D immune globulin (anti-D IGIV) is indicated for the treatment of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis (IVH) and acute renal failure (ARF) after anti-D IGIV. We report the first adu...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.10432

    authors: Chun NS,Savani B,Seder RH,Taplin ME

    更新日期:2003-12-01 00:00:00

  • Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management.

    abstract:DISEASE OVERVIEW:Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,000 new patients annually and representing approximately 11% of all lymphomas in the United States. DIAGNOSIS:HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymph...

    journal_title:American journal of hematology

    pub_type: 杂志文章,评审

    doi:10.1002/ajh.23348

    authors: Ansell SM

    更新日期:2012-12-01 00:00:00

  • Idiopathic immune-mediated acquired von Willebrand's disease in a patient with angiodysplasia: demonstration of an unusual inhibitor causing a functional defect and rapid clearance of von Willebrand factor.

    abstract::A case of idiopathic immune-mediated von Willebrand's disease (AvWD) associated angiodysplasia and recurrent lower gastrointestinal bleeding is reported. Coagulation parameters at presentation were activated partial thromboplastin time of 41 sec, bleeding time >15 min, factor VIII procoagulant activity, 5%; von Willeb...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199902)60:2<151::aid-ajh13

    authors: Alhumood SA,Devine DV,Lawson L,Nantel SH,Carter CJ

    更新日期:1999-02-01 00:00:00

  • Potentiation of vincristine cytotoxicity by hormones: corticosteroids, androgens, estrogens and progestins.

    abstract::Using an in vitro system to evaluate the simultaneous use of two drugs, we previously have confirmed the synergism of vincristine and prednisolone cytotoxicity against lymphoid cells. Experiments were now carried out to determine whether other steroid hormones can be substituted for prednisolone. Partial or complete p...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830050405

    authors: Rosner F,Hirshaut Y,Grünwald HW,Deutsch S

    更新日期:1978-01-01 00:00:00

  • Severe acute thrombocytopenia following infusion of plasma containing anti P1A1.

    abstract::An 18-year-old girl with a preoperative platelet count of 216,000/cmm received 3 units of stored plasma at the time of surgery. Within 6 hours her platelet count had fallen to 5,000/mm3 and hemorrhagic manifestations appeared. One of the plasma donors was found to be P1A1 negative with an anti P1A1 antibody. The recip...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830250213

    authors: Nijjar TS,Bonacosa IA,Israels LG

    更新日期:1987-06-01 00:00:00

  • Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death.

    abstract::Eosinophilia may represent an early paraclinical sign of hematological malignant disease, but no reports exist on its predictive value for hematological malignancies. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count (DIF...

    journal_title:American journal of hematology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/ajh.23515

    authors: Andersen CL,Siersma VD,Hasselbalch HC,Lindegaard H,Vestergaard H,Felding P,de Fine Olivarius N,Bjerrum OW

    更新日期:2013-10-01 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

  • Elevated plasma endothelin-1 levels in sickle cell anemia: relationships to oxygen saturation and left ventricular hypertrophy.

    abstract::Endothelin-1 (Et-1) is a vasoconstrictor produced by endothelial and vascular smooth muscle cells in response to hypoxia, which induces hypertrophy in cultured cardiac myocytes. We measured plasma Et-1 levels and left ventricular dimensions in 13 patients with sickle cell anemia (SCD) and in 12 African-American contro...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199807)58:3<195::aid-ajh6>

    authors: Werdehoff SG,Moore RB,Hoff CJ,Fillingim E,Hackman AM

    更新日期:1998-07-01 00:00:00

  • Incidence of ATRX mutations in myelodysplastic syndromes, the value of microcytosis.

    abstract::Acquired α-thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assess...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.24073

    authors: Herbaux C,Duployez N,Badens C,Poret N,Gardin C,Decamp M,Eclache V,Daliphard S,Murati A,Cony-Makhoul P,Cheze S,Beve B,Lacoste C,Prebet T,Hunault-Berger M,Maloisel F,Renneville A,Figeac M,Stamatoullas-Bastard A,Bastar

    更新日期:2015-08-01 00:00:00

  • The hope and reality of long-acting hemophilia products.

    abstract::Recombinant DNA technology and protein engineering are creating hope that we can address ongoing challenges in hemophilia care such as reducing the costs of therapy, increasing the availability to the developing world, and improving the functional properties of these proteins. Technological advances to improve the hal...

    journal_title:American journal of hematology

    pub_type: 杂志文章,评审

    doi:10.1002/ajh.23146

    authors: Pipe SW

    更新日期:2012-05-01 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

  • High-level, stable expression of blood group antigens in a heterologous system.

    abstract::The detection and identification of blood group antibodies in patients is crucial for successful allogeneic blood transfusions. Current methods are highly subjective and rely on red blood cells (RBCs), which simultaneously express many blood group antigens, have a short shelf-life, and carry potential biohazard risks....

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(200003)63:3<114::aid-ajh2>

    authors: Yazdanbakhsh K,Oyen R,Yu Q,Lee S,Antoniou M,Chaudhuri A,Reid ME

    更新日期:2000-03-01 00:00:00

  • Pre-eminence and persistence of immature natural killer cells in acute myeloid leukemia patients in first complete remission.

    abstract::Despite substantial progress in the treatment of AML, a proportion of patients do not achieve first complete remission (1(st) CR) with the induction chemotherapy, and, among patients achieving it, a majority is expected to relapse within three years. As allogeneic hematopoietic stem cell transplantation has been estab...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.21906

    authors: Dauguet N,Récher C,Demur C,Fournié JJ,Poupot M,Poupot R

    更新日期:2011-02-01 00:00:00

  • Development of rheumatoid arthritis after treatment of large granular lymphocyte leukemia with deoxycoformycin.

    abstract::The association of T-cell large granular lymphocyte (LGL) leukemia and rheumatoid arthritis is well described and it is now recognized that these patients and patients with Felty's syndrome represent different aspects of a single disease process. Most patients have rheumatoid arthritis at the time of diagnosis of LGL ...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199803)57:3<253::aid-ajh14

    authors: Yoe J,Gause BL,Curti BD,Longo DL,Bagg A,Kopp WC,Janik JE

    更新日期:1998-03-01 00:00:00

  • Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus.

    abstract::Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirtee...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/(sici)1096-8652(199710)56:2<93::aid-ajh4>3

    authors: Reverter JL,Reverter JC,Tàssies D,Rius F,Monteagudo J,Rubiés-Prat J,Escolar G,Ordinas A,Sanmarti A

    更新日期:1997-10-01 00:00:00

  • Kinetics of platelet density subpopulations in splenectomized mongrel dogs.

    abstract::Autologous 51Cr-platelet kinetic studies were performed in splenectomized mongrel dogs. Mean survival time of PRP-platelets was 5.4 +/- 1.5 (SD) days (n = 6). The curves, though slightly curvilinear, showed mostly a linear type of decay, denoting that platelet removal from the circulation is mainly determined by aging...

    journal_title:American journal of hematology

    pub_type: 杂志文章

    doi:10.1002/ajh.2830170407

    authors: Mezzano D,Aranda E,Foradori A,Rodríguez S,Lira P

    更新日期:1984-01-01 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