Abstract:
:c-MYC inhibits differentiation and regulates the process by which cells acquire biomass, cell growth. Down-regulation of c-MYC, reduced cell growth, and decreased activity of the PI3K/AKT/mTORC1 signal transduction pathway are features of the terminal differentiation of committed myeloid precursors to polymorphonuclear neutrophils. Since mTORC1 regulates growth, we hypothesized that pharmacological inhibition of mTORC1 by rapamycin may reverse the phenotypic effects of c-MYC. Here we show that granulocytes blocked in their ability to differentiate by enforced expression of c-MYC can be induced to differentiate by reducing exogenous c-MYC expression through rapamycin treatment. Rapamycin also reduced expression of endogenous c-MYC and resulted in enhanced retinoid-induced differentiation. Total cellular c-Myc mRNA and c-MYC protein stability were unchanged by rapamycin, however the amount of c-Myc mRNA associated with polysomes was reduced. Therefore rapamycin limited expression of c-MYC by inhibiting c-Myc mRNA translation. These findings suggest that mTORC1 could be targeted to promote terminal differentiation in myeloid malignancies characterized by dysregulated expression of c-MYC.
journal_name
Bloodjournal_title
Bloodauthors
Wall M,Poortinga G,Hannan KM,Pearson RB,Hannan RD,McArthur GAdoi
10.1182/blood-2007-09-111856subject
Has Abstractpub_date
2008-09-15 00:00:00pages
2305-17issue
6eissn
0006-4971issn
1528-0020pii
blood-2007-09-111856journal_volume
112pub_type
杂志文章相关文献
BLOOD文献大全abstract::Chronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-06-2073
更新日期:2004-03-15 00:00:00
abstract::Allogeneic stem cell transplantation (SCT) is now a commonplace procedure. Clinicians who care for patients with hematologic malignancies and aplastic anemia are almost certain to follow up patients after SCT. This review is intended to help clinicians observe patients for probably the most important late complication...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood.v97.5.1196
更新日期:2001-03-01 00:00:00
abstract::ETS2 and ERG are transcription factors, encoded on human chromosome 21 (Hsa21), that have been implicated in human cancer. People with Down syndrome (DS), who are trisomic for Hsa21, are predisposed to acute megakaryoblastic leukemia (AMKL). DS-AMKL blasts harbor a mutation in GATA1, which leads to loss of full-length...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-08-174813
更新日期:2009-04-02 00:00:00
abstract::The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipien...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-06-2325
更新日期:2006-02-01 00:00:00
abstract::Chronic lymphocytic leukemia of B-cell origin (B-CLL) is generally thought to arise by neoplastic transformation of B lymphocytes, which express CD5 and have features of an early stage of B-cell differentiation. To study isotype-switched B-CLL as a potentially more differentiated variant, we performed genetic and func...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::Detachment of individual sickle erythrocytes from cultured endothelial cell monolayers has been evaluated by a fluid-shearing technique in an effort to quantitate adherence at shear forces that would be anticipated in the in vivo circulation. Nonirreversibly sickled cells (non-ISC) were more adherent at normal oxygen ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
abstract::Plasma glutathione peroxidase (GSHPx) (glutathione: H2O2 oxidoreductase) is a unique selenoglycoprotein. Treatment of this enzyme with glycopeptidase F partially deglycosylates it and establishes the presence of N-linked sugar moieties. Antibodies raised in a rabbit against the purified enzyme from plasma were found t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::This study reassesses the occurrence of Epstein-Barr virus (EBV) diversity and coinfection versus dominance of a single viral strain within immunocompetent normal carriers. Polymerase chain reaction analysis of several different polymorphic loci of the EBV genome was performed on collections of peripheral blood mononu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract::A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::Activation of intracellular signaling pathways is important for cellular transformation and tumorigenesis. The nonreceptor tyrosine kinases Jak1 and Jak3, which bind to the v-Abl oncoprotein, are constitutively activated in cells transformed with the Abelson murine leukemia virus. A mutant of p160 v-Abl lacking the Ja...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.3.966
更新日期:2002-08-01 00:00:00
abstract::De novo erythroleukemia (EL) is a rare disease. Reported median survival are poor and vary from 4 to 14 months. The value of hematopoietic stem cell transplantation (HSCT) for EL is unknown. This EBMT registry study reports on the largest series of patients with EL treated with HSCT in first complete remission-103 aut...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood.V100.9.3135
更新日期:2002-11-01 00:00:00
abstract::Drug-dependent antibodies (DDAbs) can cause the precipitous destruction of platelets if a patient is exposed to the drug for which the antibodies are specific. The molecular character of the epitopes recognized is poorly understood, and the mechanism by which drugs promote tight binding of these antibodies to platelet...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-07-2336
更新日期:2003-02-01 00:00:00
abstract::Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation....
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::Tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 are proteins with proteinase-inhibiting and cytokine properties. TIMP-1 is active primarily in B cells and B-cell lymphomas, whereas TIMP-2 expression is restricted to T cells. The expression of TIMP-1 and TIMP-2 in lymph nodes from patients with Hodgkin disea...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.1.258
更新日期:2002-01-01 00:00:00
abstract::Treatment of AL amyloidosis patients with high-dose melphalan chemotherapy followed by autologous peripheral blood stem cell transplantation (HDM/SCT) can produce hematologic complete responses (CRs) and improvement in organ function. To determine whether these responses are accompanied by improvement in quality of li...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2004-01-0089
更新日期:2004-09-15 00:00:00
abstract::Interleukin-10 (IL-10) selectively inhibited lipopolysaccharide (LPS)-induced chemoattractant cytokine gene expression: levels of IP-10 mRNA were markedly suppressed in IL-10-treated mouse peritoneal macrophages, whereas the expression of the RANTES mRNA was only modestly reduced. IL-10 inhibited IP-10 mRNA accumulati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-15 00:00:00
abstract::Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder characterized by lesions composed of pathological CD207(+) dendritic cells with an inflammatory infiltrate. BRAFV600E remains the only recurrent mutation reported in LCH. In order to evaluate the spectrum of somatic mutations in LCH, whole exome sequ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-05-577825
更新日期:2014-11-06 00:00:00
abstract::Overactivated complement is a high-risk feature in hematopoietic stem cell transplant (HSCT) recipients with transplant-associated thrombotic microangiopathy (TA-TMA), and untreated patients have dismal outcomes. We present our experience with 64 pediatric HSCT recipients who had high-risk TA-TMA (hrTA-TMA) and multio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019004218
更新日期:2020-03-26 00:00:00
abstract::Efficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that macrophage colony-stimulating factor (M-CSF)-driven macrophages (Mø2s) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This ma...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4144
更新日期:2006-06-15 00:00:00
abstract::The large granular lymphocyte (LGL) population, which effects a natural killer (NK) function, consists of cells whose lineage derivation has not been clearly established on the basis of phenotypic and functional properties. To clarify the relationship of LGL/NK cells to T cells we studied patterns of rearrangement and...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Production of tumor necrosis factor-alpha (TNFalpha) by the neutrophil (PMN) is a pivotal event in innate immunity, but the signals regulating TNFalpha induction in this primary cell are poorly understood. Herein, we use protein transduction to identify novel, opposing anti- and pro-cytokine-inducing roles for RhoA in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-03-012898
更新日期:2007-02-01 00:00:00
abstract::In this issue of Blood, Buchlis and colleagues describe the long-term persistence (up to 10 years) of factor IX (FIX) expression in adeno-associated virus serotype 2 (AAV-2)–injected muscles of a patient with hemophilia B. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2012-02-409086
更新日期:2012-03-29 00:00:00
abstract::B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin V(H) genes have better outcome than unmutated cases. V(H)-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the progn...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-11-4394
更新日期:2005-06-15 00:00:00
abstract::Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. The molecular mechanisms underlying stem cell trafficking are poorly defined. Based on a short hairpin RNA library and stromal cell-derived factor-1 (SDF-1) migration screening assay, we identified the histone 3 lysine 27 demethylase UTX...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-452003
更新日期:2013-03-28 00:00:00
abstract::The nature of cells present in the blood, marrow, and spleen of patients with hairy cell leukemia is largely debated. These cells have been tentatively categorized on the basis of either monocytic or lymphocytic markers, and the accumulating data points to the fact that they share some characteristics of both cell typ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1978-09-01 00:00:00
abstract::Arsenic trioxide, as a single agent, has proven efficacy in inducing molecular remission in patients with acute promyelocytic leukemia (APL). There is limited long-term outcome data with single-agent As2O3 in the management of newly diagnosed cases of APL. Between January 1998 to December 2004, 72 newly diagnosed case...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2005-08-3532
更新日期:2006-04-01 00:00:00
abstract::By using an enzyme-linked immunosorbent assay, the presence of the soluble form of the interleukin-2 receptor (sIL-2R) was evaluated in the peripheral blood of 54 patients with B cell chronic lymphocytic leukemia (B-CLL). Serum levels of sIL-2R were correlated with clinical features, relevant hematologic and immunolog...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Sickle cell trait (SCT) is unique among the carrier states that are identified during newborn screening. Unlike other heterozygous states for rare recessive diseases, SCT is exceedingly prevalent throughout regions of the world, making sickle cell disease one of the most common monogenetic diseases worldwide. Because ...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2018-06-848705
更新日期:2018-11-29 00:00:00
abstract::T-cell progenitors in the embryonic bone marrow express the tyrosine kinase receptor c-kit. RR5, an anti-MHC class II beta chain monoclonal antibody, subdivides this c-kit positive population. Intrathymic transfer experiments showed that most of the T-cell progenitors belong to the MHC class II(+)/c-kit(+) bone marrow...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Fibrinogen was isolated from the plasma of a 25-year-old female with a history of mild bleeding and several recent moderate to severe hemorrhagic episodes. Coagulability with thrombin approached 100% and varied directly with the time of incubation with the enzyme. High-performance liquid chromatography analysis of thr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00