Abstract:
:Myelodysplastic syndromes (MDSs) are hematopoietic stem cell disorders in which recurrent mutations define clonal hematopoiesis. The origin of the phenotypic diversity of non-del(5q) MDS remains unclear. Here, we investigated the clonal architecture of the CD34+CD38- hematopoietic stem/progenitor cell (HSPC) compartment and interrogated dominant clones for MDS-initiating cells. We found that clones mainly accumulate mutations in a linear succession with retention of a dominant subclone. The clone detected in the long-term culture-initiating cell compartment that reconstitutes short-term human hematopoiesis in xenotransplantation models is usually the dominant clone, which gives rise to the myeloid and to a lesser extent to the lymphoid lineage. The pattern of mutations may differ between common myeloid progenitors (CMPs), granulomonocytic progenitors (GMPs), and megakaryocytic-erythroid progenitors (MEPs). Rare STAG2 mutations can amplify at the level of GMPs, from which it may drive the transformation to acute myeloid leukemia. We report that major truncating BCOR gene mutation affecting HSPC and CMP was beneath the threshold of detection in GMP or MEP. Consistently, BCOR knock-down (KD) in normal CD34+ progenitors modifies their granulocytic and erythroid differentiation. Clonal architecture of the HSPC compartment and mutations selected during differentiation contribute to the phenotypic heterogeneity of MDS. Defining the hierarchy of driver mutations provides insights into the process of transformation and may guide the search for novel therapeutic strategies.
journal_name
Bloodjournal_title
Bloodauthors
Chesnais V,Arcangeli ML,Delette C,Rousseau A,Guermouche H,Lefevre C,Bondu S,Diop M,Cheok M,Chapuis N,Legros L,Raynaud S,Willems L,Bouscary D,Lauret E,Bernard OA,Kosmider O,Pflumio F,Fontenay Mdoi
10.1182/blood-2016-03-707745subject
Has Abstractpub_date
2017-01-26 00:00:00pages
484-496issue
4eissn
0006-4971issn
1528-0020pii
blood-2016-03-707745journal_volume
129pub_type
杂志文章相关文献
BLOOD文献大全abstract::The loss of body cell mass (bcm) in senescence and wasting is poorly understood. We now show that the plasma cystine/acid soluble thiol ratio, ie, an indicator of the redox state, is increased in old age and cancer patients and correlated with a decrease in bcm and plasma albumin. A cause/effect relationship was sugge...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-07-01 00:00:00
abstract::Sickle cell anemia (SCA) is an inherited disorder of beta-globin, resulting in red blood cell rigidity, anemia, painful crises, organ infarctions, and reduced life expectancy. Allogeneic blood or marrow transplantation (BMT) can cure SCA but is associated with an 8% to 10% mortality rate, primarily from complications ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.12.3960
更新日期:2001-06-15 00:00:00
abstract::Primary mediastinal large B-cell lymphoma (PMBCL) is a recognized non-Hodgkin lymphoma entity with unique pathologic, clinical, and molecular characteristics distinct from those of other diffuse large B-cell lymphomas. Immunohistochemical characterization and molecular studies strongly suggest that PMBCL is of germina...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2011-05-326538
更新日期:2011-09-08 00:00:00
abstract::We have analyzed the reactivation of fetal hemoglobin (HbF) synthesis under rigorous in vitro conditions, ie, in mature erythroblasts generated by erythroid burst-forming units (BFU-E) stringently purified from normal adult peripheral blood and grown in fetal calf serum(FCS)-free semisolid or liquid phase culture. In ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-01-15 00:00:00
abstract::The events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSCs) after transplantation are not well defined. We report for the first time that major histocompatibility complex (MHC) class I K plays a critical role in HSC engraftment via interaction with recipient natural kille...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-11-3910
更新日期:2004-08-01 00:00:00
abstract::Human herpesvirus 8 (HHV-8) genomic sequences were recently detected by polymerase chain reaction (PCR) and in situ hybridization in bone marrow stromal cells grown from multiple myeloma (MM) patients, but not in cells from control subjects (Rettig et al, Science 276:1851, 1997). We sought to confirm these observation...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-10-15 00:00:00
abstract::Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibalpha. Three polymorphisms have been described in GP Ibalpha (Kozak T/C polymorphism, variable number of tandem ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.1.36
更新日期:2001-07-01 00:00:00
abstract::The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM c...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-279893
更新日期:2010-10-28 00:00:00
abstract::The PI3K/Akt/mTOR pathway has emerged as a critical regulator of dendritic cell (DC) development and function. The kinase mTOR is found in 2 distinct complexes, mTORC1 and mTORC2. In this study, we show that mTORC1 but not mTORC2 is required for epidermal Langerhans cell (LC) homeostasis. Although the initial seeding ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-439786
更新日期:2013-01-10 00:00:00
abstract::Insulin-like growth factor 1 (IGF-1) enhances thymopoiesis but given the broad distribution of IGF-1 receptors (IGF-1Rs), its mechanism of action has remained unclear. To identify points of thymic regulation by IGF-1, we examined its effects on T-cell precursors, thymocytes, and thymic epithelial cells (TECs) in norma...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-04-149435
更新日期:2008-10-01 00:00:00
abstract::Follicular dendritic cells (FDCs) in the lymphoid follicle (LF) are essential to the sequential processes of B-cell proliferation, selection, and differentiation. Although the importance of some cytokines in these processes has been pointed out, there is little information about the follicular localization of their re...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-12-15 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::Absorption of iron was studied with a double-isotope technique that allowed differentiation between "mucosal uptake," "mucosal transfer," and ultimate "retention" of iron. A physiologic dose of ferrous sulfate was administered to 25 healthy young adults, 40 active aged persons, and 20 patients with uncomplicated iron ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::Kaposi's sarcoma-associated herpes virus (KSHV)/human herpes virus 8 (HHV8) DNA sequences have been demonstrated in Kaposi's sarcoma (KS), as well as in some acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (NHL) and in multicentric Castleman's disease. Although KSHV DNA generally is abundant ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::Highly purified natural killer (NK) cell suspensions were tested for their capacity to release colony-stimulating activity (CSA) in vitro. NK cell suspensions comprised primarily CD16+ cells and were devoid of CD3+ T cells, CD15+ monocytes, and of B cells. CSA was detected in the NK cell supernatants and sustained the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase 1 testing in relapsed/refractory hairy cell leukemia (HCL; n = 28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 dose...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-09-803072
更新日期:2018-05-24 00:00:00
abstract::Using age-fractionated erythrocytes, warm autoantibodies can be classified into two distinct categories, depending on their reactivity with reticulocyte-enriched (younger) or reticulocyte-poor (older) red cell fractions. The strength of the direct antiglobulin test (DAT) on the age-fractionated red cells of 24 patient...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::BRCA1 is critical for maintenance of genomic stability and interacts directly with several proteins that regulate hematopoietic stem cell function and are part of the Fanconi anemia (FA) double-strand break DNA repair pathway. The effects of complete BRCA1 deficiency on bone marrow (BM) function are unknown. To test t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-03-635599
更新日期:2016-01-21 00:00:00
abstract::Techniques for the quantitation of virus-specific and alloantigen-reactive T cells vary in their measurement of clinically relevant T-cell effector populations, their sensitivity and quantitative accuracy, and the time required to obtain measurable results. We compared frequencies of Epstein-Barr virus (EBV)-specific ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.5.1730
更新日期:2002-03-01 00:00:00
abstract::The dendritic cell (DC)-specific molecule DC-SIGN is a receptor for the HIV-1 envelope glycoprotein gp120 and is essential for the dissemination of HIV-1. DC-SIGN is expressed by DCs, both monocyte-derived DCs and DCs in several tissues, including mucosa and lymph nodes. To identify a DC-SIGN(+) DC in blood that may b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2001-12-0179
更新日期:2002-09-01 00:00:00
abstract::Patients after allogeneic stem-cell transplantation (alloSCT) have an increased risk for invasive aspergillosis (IA). Here, recipients of an allograft with IA (n=81) or without IA (n=58) were screened for 84 single nucleotide polymorphisms in 18 immune relevant genes. We found 3 markers in chemokine (C-X-C motif) liga...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2007-05-090928
更新日期:2008-01-15 00:00:00
abstract::Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by deplet...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::High concentrations of bovine factor VIII cause clumping of platelets into a few very large aggregates. This response is termed superaggregation. It is distinct from factor-VIII-induced agglutination but is also independent of both extracellular calcium ions and platelet energy metabolism. Neither agglutinating lectin...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-12-01 00:00:00
abstract::Recombinant (r) and natural human (h) macrophage colony-stimulating factor (M-CSF, CSF-1) have been considered poor stimulators of macrophage progenitor cells present in human marrow, although they are potent stimulators of these cells in mouse marrow. We compared the growth characteristics of rhM-CSF-responsive human...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-07-15 00:00:00
abstract::We have studied the impact of B-cell receptor (BCR) or CD40 ligation on the in vitro chemotactic response of tonsillar B cells to 4 chemokines: stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and B-cell-attracting chemokine (BCA)-1. In the tonsil, SDF-1 and MIP-3alpha...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.6.1913
更新日期:2002-03-15 00:00:00
abstract::The promising activity of BET protein inhibitors (BETi's) is compromised by adaptive or innate resistance in acute myeloid leukemia (AML). Here, modeling of BETi-persister/resistance (BETi-P/R) in human postmyeloproliferative neoplasm (post-MPN) secondary AML (sAML) cells demonstrated accessible and active chromatin i...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019002922
更新日期:2020-04-09 00:00:00
abstract::In this report, we describe a modification of the assay for long-term culture-initiating cells (LTC-IC) that allows a subset of murine LTC-IC (designated as LTC-ICML) to express both their myeloid (M) and lymphoid (L) differentiative potentials in vitro. The modified assay involves culturing test cells at limiting dil...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-08-15 00:00:00
abstract::The molecular backgrounds of variants encountered in Afro-Caribbean black individuals and associated with the production of clinically significant antibodies against high-incidence antigens (anti-RH18, anti-RH34) and against Rhe epitopes were determined. We showed that RH:-18 phenotypes are produced by 3 distinct RHCE...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0229
更新日期:2002-12-01 00:00:00
abstract::Acute chest syndrome (ACS) is a leading cause of death in sickle cell disease (SCD). Our previous work showed that hypoxia enhances the ability of sickle erythrocytes to adhere to human microvessel endothelium via interaction between very late activation antigen-4 (VLA4) expressed on sickle erythrocytes and the endoth...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00