Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes.

Abstract:

:Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease is associated with loss-of-function mutations in the SBDS gene, implicated in ribosome biogenesis, but the cellular and molecular events driving cell specific phenotypes in ribosomopathies remain poorly defined. Here, we established what is to our knowledge the first mammalian model of neutropenia in Shwachman-Diamond syndrome through targeted downregulation of Sbds in hematopoietic stem and progenitor cells expressing the myeloid transcription factor CCAAT/enhancer binding protein α (Cebpa). Sbds deficiency in the myeloid lineage specifically affected myelocytes and their downstream progeny while, unexpectedly, it was well tolerated by rapidly cycling hematopoietic progenitor cells. Molecular insights provided by massive parallel sequencing supported cellular observations of impaired cell cycle exit and formation of secondary granules associated with the defect of myeloid lineage progression in myelocytes. Mechanistically, Sbds deficiency activated the p53 tumor suppressor pathway and induced apoptosis in these cells. Collectively, the data reveal a previously unanticipated, selective dependency of myelocytes and downstream progeny, but not rapidly cycling progenitors, on this ubiquitous ribosome biogenesis protein, thus providing a cellular basis for the understanding of myeloid lineage biased defects in Shwachman-Diamond syndrome.

journal_name

Haematologica

journal_title

Haematologica

authors

Zambetti NA,Bindels EM,Van Strien PM,Valkhof MG,Adisty MN,Hoogenboezem RM,Sanders MA,Rommens JM,Touw IP,Raaijmakers MH

doi

10.3324/haematol.2015.131573

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

1285-93

issue

10

eissn

0390-6078

issn

1592-8721

pii

haematol.2015.131573

journal_volume

100

pub_type

杂志文章
  • Hemoglobin sickle cell disease complications: a clinical study of 179 cases.

    abstract:BACKGROUND:Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease. D...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.055202

    authors: Lionnet F,Hammoudi N,Stojanovic KS,Avellino V,Grateau G,Girot R,Haymann JP

    更新日期:2012-08-01 00:00:00

  • Efficient generation and characterization of tumor cell subclones with different adhesion pathways involved in cell lysis.

    abstract:BACKGROUND:Specific tumor cell recognition is required for optimal tumor directed therapy. Lymphokine activated killer (LAK) cells are able to recognize tumor targets specifically because LAK cells can distinguish between normal and tumor cells. This study was aimed at analyzing receptor molecules on tumor cells and th...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Lefterova P,Negrin R,Neubauer A,Huhn D,Blume K,Schmidt-Wolf I

    更新日期:1993-11-01 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

  • Inversion mutation as a major cause of severe hemophilia A in Italian patients.

    abstract::We investigated the presence of a recombinant event between the F8A gene located in intron 22 of the factor VIII gene and the two additional copies of F8A lying 500 Kb upstream of FVIII in severe hemophilic patients. The genomic DNA of 146 unrelated Italian patients with severe hemophilia A (HA) was hybridized with an...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Mori PG,Caprino D,Bicocchi MP,Valetto A,Bottini F,Aquila M

    更新日期:1997-01-01 00:00:00

  • Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases.

    abstract:BACKGROUND:Relapsing primary central nervous system lymphoma carries a poor prognosis when treated with conventional chemotherapy with a one-year overall survival of 25-40%. Encouraging results have been shown with intensive chemotherapy followed by autologous hematopoietic stem cell rescue. We report the results of a ...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:10.3324/haematol.2011.060434

    authors: Soussain C,Choquet S,Fourme E,Delgadillo D,Bouabdallah K,Ghesquières H,Damaj G,Dupriez B,Vargaftig J,Gonzalez A,Houillier C,Taillandier L,Hoang-Xuan K,Leblond V

    更新日期:2012-11-01 00:00:00

  • MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response.

    abstract:BACKGROUND:MicroRNAs can play an important role in tumorigenesis through post-transcriptional regulation of gene expression, and are not well characterized in follicular lymphoma. DESIGN AND METHODS:MicroRNA profiles of enriched follicular lymphoma tumor cells from 16 patients were generated by assaying 851 human micr...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.048132

    authors: Wang W,Corrigan-Cummins M,Hudson J,Maric I,Simakova O,Neelapu SS,Kwak LW,Janik JE,Gause B,Jaffe ES,Calvo KR

    更新日期:2012-04-01 00:00:00

  • Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation.

    abstract:BACKGROUND AND OBJECTIVES:Whether human mesenchymal stem cells (MSC) can be transplanted is controversial and their presence in peripheral blood is not fully accepted. In the present study we have analyzed whether, within the allogeneic transplantation setting, MSC are of host or donor origin. DESIGN AND METHODS:Bone ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Villaron EM,Almeida J,López-Holgado N,Alcoceba M,Sánchez-Abarca LI,Sanchez-Guijo FM,Alberca M,Pérez-Simon JA,San Miguel JF,Del Cañizo MC

    更新日期:2004-12-01 00:00:00

  • Management of multiple myeloma and related-disorders: guidelines from the Italian Society of Hematology (SIE), Italian Society of Experimental Hematology (SIES) and Italian Group for Bone Marrow Transplantation (GITMO).

    abstract:OBJECTIVES:Perceiving the need for rigorous recommendations to facilitate decisions concerning the management of patients with multiple myeloma (MM), the Italian Society of Hematology (SIE) and the two affiliate societies (SIES and GITMO) commissioned a project to develop guidelines for the therapy of MM using evidence...

    journal_title:Haematologica

    pub_type: 杂志文章,实务指引,评审

    doi:

    authors: Barosi G,Boccadoro M,Cavo M,Corradini P,Marchetti M,Massaia M,Merlini G,Tosi P,Tura S,Italian Society of Hematology.,Italian Society of Experimental Hematology.,Italian Group for Bone Marrow Transplantation.

    更新日期:2004-06-01 00:00:00

  • Parvovirus B19 infections in patients with chronic anemia.

    abstract:BACKGROUND AND OBJECTIVE:Parvovirus B19 has a marked tropism for erythroid progenitor cells and this may lead to chronic anemia in predisposed individuals. It was the purpose of the present study to investigate prospectively the frequency of parvovirus B19 infections in patients with a diagnosis of chronic anemia. MET...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Heegaard ED,Myhre J,Hornsleth A,Gundestrup M,Boye H

    更新日期:1997-07-01 00:00:00

  • Hematocrit and risk of venous thromboembolism in a general population. The Tromso study.

    abstract:BACKGROUND:Hematocrit above the normal range for the population, such as in primary or secondary erythrocytosis, predisposes to both arterial and venous thrombosis. However, little is known about the association between hematocrit and risk of venous thromboembolism in a general population. DESIGN AND METHODS:Hematocri...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2009.008417

    authors: Braekkan SK,Mathiesen EB,Njølstad I,Wilsgaard T,Hansen JB

    更新日期:2010-02-01 00:00:00

  • The association of cyclophosphamide and dexamethasone in advanced refractory multiple myeloma patients.

    abstract::VAD is the most active regimen in refractory myeloma patients; however, the role of vincristine and doxorubicin remains unclear. Relatively high doses of cyclophosphamide (3.6 g/sqm) increased the response rate and survival in resistant MM. Cyclophosphamide and dexamethasone were administered to 28 patients with advan...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Celesti L,Clavio M,Poggi A,Casciaro S,Vallebella E,Gobbi M

    更新日期:1997-05-01 00:00:00

  • Clinical features and laboratory patterns in a cohort of consecutive Argentinian patients with von Willebrand's disease.

    abstract:BACKGROUND AND OBJECTIVES:von Willebrand's disease (vWD) is a bleeding disorder with variable clinical expression. Our aim was to classify patients with vWD and to determine the phenotype in their relatives. DESIGN AND METHODS:The types and subtypes, blood group frequency and its relevance, bleeding sites, response to...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Woods AI,Meschengieser SS,Blanco AN,Salviú MJ,Farías CE,Kempfer AC,Lazzari MA

    更新日期:2001-04-01 00:00:00

  • Expression of the c-Met oncogene by tumor cells predicts a favorable outcome in classical Hodgkin's lymphoma.

    abstract:BACKGROUND:The c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Deregulated c-Met activation has been implicated in the pathogenesis and prognosis of many human malignancies. We studied the function and prognostic significance of c-Met and hepatocyte ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.056101

    authors: Xu C,Plattel W,van den Berg A,Rüther N,Huang X,Wang M,de Jong D,Vos H,van Imhoff G,Viardot A,Möller P,Poppema S,Diepstra A,Visser L

    更新日期:2012-04-01 00:00:00

  • ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells.

    abstract::Successful expansion of hematopoietic stem cells would benefit the use of hematopoietic stem cell transplants in the clinic. Several angiopoietin-like proteins, including angiopoietin-like 7, can support the activity of hematopoietic stem cells. However, effects of ANGPTL7 on human hematopoietic stem cells and the dow...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2014.118612

    authors: Xiao Y,Jiang Z,Li Y,Ye W,Jia B,Zhang M,Xu Y,Wu D,Lai L,Chen Y,Chang Y,Huang X,Liu H,Qing G,Liu P,Li Y,Xu B,Zhong M,Yao Y,Pei D,Li P

    更新日期:2015-05-01 00:00:00

  • Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features.

    abstract::In childhood B-cell precursor acute lymphoblastic leukemia, cytogenetics is important in diagnosis and as an indicator of response to therapy, thus playing a key role in risk stratification of patients for treatment. Little is known of the relationship between different cytogenetic subtypes in B-cell precursor acute l...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.3324/haematol.2013.085175

    authors: Schwab CJ,Chilton L,Morrison H,Jones L,Al-Shehhi H,Erhorn A,Russell LJ,Moorman AV,Harrison CJ

    更新日期:2013-07-01 00:00:00

  • Recurrent mutations in the iron regulatory element of L-ferritin in hereditary hyperferritinemia-cataract syndrome.

    abstract:BACKGROUND AND OBJECTIVE:Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder characterized by bilateral cataracts and increased serum and tissue L-ferritin, in the absence of iron overload. The deregulation of ferritin production is caused by heterogeneous mutations in the iron regul...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Cicilano M,Zecchina G,Roetto A,Bosio S,Infelise V,Stefani S,Mazza U,Camaschella C

    更新日期:1999-06-01 00:00:00

  • Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia.

    abstract::Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of yo...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章

    doi:10.3324/haematol.2017.166215

    authors: Papaioannou D,Nicolet D,Volinia S,Mrózek K,Yan P,Bundschuh R,Carroll AJ,Kohlschmidt J,Blum W,Powell BL,Uy GL,Kolitz JE,Wang ES,Eisfeld AK,Orwick SJ,Lucas DM,Caligiuri MA,Stone RM,Byrd JC,Garzon R,Bloomfield CD

    更新日期:2017-08-01 00:00:00

  • The natural history of trilinear myelodysplastic syndrome and erythroleukemia.

    abstract::A case of Di Guglielmo's syndrome passed through the three stages of chronic erythromyelosis, erythroleukemia and acute myeloid leukemia (AML). According to the FAB classification the subsequent stages of this syndrome were refractory anemia (RA), RA with excess of blasts (RAEB), AML-M6, AML-M2 and undifferentiated AM...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Michiels JJ,van der Meulen J,Brederoo P

    更新日期:1997-07-01 00:00:00

  • Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparticles in patients with a previous myocardial infarction.

    abstract:BACKGROUND:Increased levels of microparticles exposing tissue factor circulate in the blood of patients with coronary heart disease, possibly disseminating their pro-thrombotic and pro-inflammatory potential. Because diets rich in n-3 (polyunsaturated) fatty acids have been associated with reduced incidence of coronary...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.11845

    authors: Del Turco S,Basta G,Lazzerini G,Evangelista M,Rainaldi G,Tanganelli P,Christensen JH,Schmidt EB,De Caterina R

    更新日期:2008-06-01 00:00:00

  • Role of hepatocyte growth factor in the development of dendritic cells from CD34+ bone marrow cells.

    abstract:BACKGROUND AND OBJECTIVE:Hepatocyte growth factor (HGF) is known to augment the effects of stem cell factor, interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoetin, and granulocyte colony-stimulating factor, all of which are involved in hematopoiesis. HGF is also known to have a role in...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Ovali E,Ratip S,Kibaroglu A,Tekelioglu Y,Cetiner M,Karti S,Aydin F,Bayik M,Akoglu T

    更新日期:2000-05-01 00:00:00

  • Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3).

    abstract::Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based ...

    journal_title:Haematologica

    pub_type: 杂志文章,实务指引,评审

    doi:10.3324/haematol.2012.065110

    authors: Skiada A,Lanternier F,Groll AH,Pagano L,Zimmerli S,Herbrecht R,Lortholary O,Petrikkos GL,European Conference on Infections in Leukemia.

    更新日期:2013-04-01 00:00:00

  • In vitro modulation of bcl-2 protein expression, drug-induced apoptosis and cytotoxicity by interleukin-10 in chronic lymphocytic leukemia.

    abstract::Interleukin-10 failed to modify either the percentage of bcl-2+ cells or the number of bcl-2 molecules, or to reduce 2-chlorodeoxyadenosine- and fludarabine-induced apoptosis. The cytokine at 0.1 ng/mL induced an increase of cell survival both in the absence or in the presence of 2-chlorodeoxyadenosine, while no diffe...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Morabito F,Filangeri M,Sculli G,Oliva B

    更新日期:1998-11-01 00:00:00

  • Clinicopathological analysis of malignant lymphoma in Taiwan, defined according to the World Health Organization classification.

    abstract::We report the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan, defined according to the WHO classification. Data including age and gender of the patients, clinical staging and disease courses were collected for 598 cases of malignant lymphomas. The results showed that the epidemio...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Lee MY,Tan TD,Feng AC,Liu MC

    更新日期:2005-12-01 00:00:00

  • Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study.

    abstract::Cough mixture abuse has been reported to cause severe folate deficiency and neurological defects. We carried out a prospective case-controlled survey to confirm this association and define the incidence and severity of the problem. A total of 57 cough mixture abusers and 47 other substance abusers (controls) were stud...

    journal_title:Haematologica

    pub_type: 信件

    doi:10.3324/haematol.10859

    authors: Au WY,Tsang SK,Cheung BK,Siu TS,Ma ES,Tam S

    更新日期:2007-04-01 00:00:00

  • ATM gene alterations in chronic lymphocytic leukemia patients induce a distinct gene expression profile and predict disease progression.

    abstract:BACKGROUND:The genetic characterization of chronic lymphocytic leukemia cells correlates with the behavior, progression and response to treatment of the disease. DESIGN AND METHODS:Our aim was to investigate the role of ATM gene alterations, their biological consequences and their value in predicting disease progressi...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.049270

    authors: Guarini A,Marinelli M,Tavolaro S,Bellacchio E,Magliozzi M,Chiaretti S,De Propris MS,Peragine N,Santangelo S,Paoloni F,Nanni M,Del Giudice I,Mauro FR,Torrente I,Foà R

    更新日期:2012-01-01 00:00:00

  • Severe events in donors after allogeneic hematopoietic stem cell donation.

    abstract:BACKGROUND:The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion. DESIGN AND METH...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.13668

    authors: Halter J,Kodera Y,Ispizua AU,Greinix HT,Schmitz N,Favre G,Baldomero H,Niederwieser D,Apperley JF,Gratwohl A

    更新日期:2009-01-01 00:00:00

  • Anticoagulation in the antiphospholipid syndrome.

    abstract::Our objectives were to evaluate thrombotic complications in patients with lupus anticoagulant fulfilling Sapporo criteria, anticoagulated with an intended INR 2.0-3.0 due to venous and arterial thrombosis. In our series standard anticoagulation was safe and efficacious in preventing recurrences in patients with system...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Casais P,Alberto MF,Gennari LC,Grosso SH,Meschengieser SS,Lazzari MA

    更新日期:2004-04-01 00:00:00

  • From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives.

    abstract::Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autolo...

    journal_title:Haematologica

    pub_type: 杂志文章,评审

    doi:10.3324/haematol.2017.174573

    authors: Gay F,Engelhardt M,Terpos E,Wäsch R,Giaccone L,Auner HW,Caers J,Gramatzki M,van de Donk N,Oliva S,Zamagni E,Garderet L,Straka C,Hajek R,Ludwig H,Einsele H,Dimopoulos M,Boccadoro M,Kröger N,Cavo M,Goldschmidt H,B

    更新日期:2018-02-01 00:00:00

  • CD34+ gene expression profiling of individual children with very severe aplastic anemia indicates a pathogenic role of integrin receptors and the proapoptotic death ligand TRAIL.

    abstract:UNLABELLED:BACKGROUND Very severe aplastic anemia is characterized by a hypoplastic bone marrow due to destruction of CD34(+) stem cells by autoreactive T cells. Investigation of the pathomechanism by patient-specific gene expression analysis of the attacked stem cells has previously been impractical because of the sca...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.056705

    authors: Fischer U,Ruckert C,Hubner B,Eckermann O,Binder V,Bakchoul T,Schuster FR,Merk S,Klein HU,Führer M,Dugas M,Borkhardt A

    更新日期:2012-09-01 00:00:00

  • HLA-DRB1*15 and pediatric aplastic anemia.

    abstract::We report a positive association between HLA-DRB1*15 (p= 0.0002) in Turkish patients with pediatric severe aplastic anemia (SAA) and a paradoxically favorable influence of the susceptibility marker on the clinical response to immunosuppressive therapy. These findings point to an immune mechanism mediated by DRB1*15 in...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Oguz FS,Yalman N,Diler AS,Oguz R,Anak S,Dorak MT

    更新日期:2002-07-01 00:00:00