Abstract:
:c-Myc (Myc hereafter) is found to be deregulated and/or amplified in most acute myeloid leukemias (AMLs). Almost all AML cells are dependent upon Myc for their proliferation and survival. Thus, Myc has been proposed as a critical anti-AML target. Myc has Max-mediated transactivational and Myc-interacting zinc finger protein 1 (Miz1)-mediated transrepressional activities. The role of Myc-Max-mediated transactivation in the pathogenesis of AML has been well studied; however, the role of Myc-Miz1-mediated transrepression in AML is still somewhat obscure. Myc protein harboring a V394D mutation (MycV394D) is a mutant form of Myc that lacks transrepressional activity due to a defect in its ability to interact with Miz1. We found that, compared with Myc, the oncogenic function of MycV394D is significantly impaired. The AML/myeloproliferative disorder that develops in mice receiving MycV394D-transduced hematopoietic stem/progenitor cells (HSPCs) is significantly delayed compared with mice receiving Myc-transduced HSPCs. Using a murine MLL-AF9 AML model, we found that AML cells expressing MycV394D (intrinsic Myc deleted) are partially differentiated and show reductions in both colony-forming ability in vitro and leukemogenic capacity in vivo. The reduced frequency of leukemia stem cells (LSCs) among MycV394D-AML cells and their reduced leukemogenic capacity during serial transplantation suggest that Myc-Miz1 interaction is required for the self-renewal of LSCs. In addition, we found that MycV394D-AML cells are more sensitive to chemotherapy than are Myc-AML cells. Mechanistically, we found that Myc represses Miz1-mediated expression of CCAAT/enhancer-binding protein α (Cebpα) and Cebpδ, thus playing an important role in the pathogenesis of AML by maintaining the undifferentiated state and self-renewal capacity of LSCs.
journal_name
Bloodjournal_title
Bloodauthors
Zhang L,Li J,Xu H,Shao X,Fu L,Hou Y,Hao C,Li W,Joshi K,Wei W,Xu Y,Zhang F,Dai S,Breslin P,Zhang J,Zhang Jdoi
10.1182/blood.2019001863subject
Has Abstractpub_date
2020-04-02 00:00:00pages
1133-1145issue
14eissn
0006-4971issn
1528-0020pii
441057journal_volume
135pub_type
杂志文章相关文献
BLOOD文献大全abstract::One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by mai...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical tri...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2017-07-792143
更新日期:2017-11-09 00:00:00
abstract::Heavy chain ferritin (H-ferritin) is a component of the iron-binding protein, ferritin. We have previously shown that H-ferritin inhibits anti-CD3-stimulated lymphocyte proliferation and that this was due to increased production of interleukin-10 (IL-10). In the present study we have shown that induction of IL-10 prod...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.9.3326
更新日期:2002-05-01 00:00:00
abstract::Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subs...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-07-2525
更新日期:2004-03-01 00:00:00
abstract::Ferroportin (FPN) mediates iron export from cells; FPN mutations are associated with the iron overloading disorder hemochromatosis. Previously, we found that the A77D, V162del, and G490D mutations inhibited FPN activity, but that other disease-associated FPN variants retained full iron export capability. The peptide h...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-02-0561
更新日期:2005-08-01 00:00:00
abstract::Adenovirus infections occur in 5% to 21% of patients following stem cell transplantation (SCT), with an associated mortality of up to 50%. However, a lack of prospective studies has hampered further developments in the understanding and management of this infection in the posttransplantation setting. We prospectively ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-02-0377
更新日期:2002-09-01 00:00:00
abstract::Long-term survival is now an expected outcome after hematopoietic cell transplantation (HCT). However, the burden of morbidity long-term after HCT remains unknown. We examined the magnitude of risk of chronic health conditions reported by 1022 HCT survivors and their siblings (n = 309). A severity score (grades 1 [mil...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-06-229369
更新日期:2010-10-28 00:00:00
abstract::The best initial therapy for elderly patients with chronic lymphocytic leukemia (CLL) has not yet been defined. We investigated the activity of lenalidomide as initial therapy for elderly patients with CLL. Sixty patients with CLL 65 years of age and older received treatment with lenalidomide orally 5 mg daily for 56 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-339077
更新日期:2011-09-29 00:00:00
abstract::Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increas...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by abnormal circulation and proliferation of malignant progenitors. In contrast to their normal counterparts, CML progenitors adhere poorly to bone marrow stroma or fibronectin (FN). Aside from anchoring progenitors ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-03-15 00:00:00
abstract::The tal-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor required for primitive and definitive hematopoiesis. Additionally, ectopic activation of the tal-1 gene during T lymphopoiesis occurs in numerous cases of human T-cell acute lymphoblastic leukemia. With the use of transgenic mice, we show that...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.2.491
更新日期:2002-07-15 00:00:00
abstract::Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmus...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
abstract::The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with th...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2013-09-524108
更新日期:2014-02-06 00:00:00
abstract::Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donor...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-06-01 00:00:00
abstract::The malignant monoclonal population in hairy cell leukemia (HCL) has been variously ascribed to be of myeloid, B, or even T cell origin. Recent data have been interpreted as suggesting that hairy cells (HC) may concomitantly or serially express both B and T surface determinants, a phenomenon which, if verified, would ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract::An unbalanced translocation der(1;7)(q10; p10) is a nonrandom chromosomal aberration commonly observed in myelodysplastic syndrome and acute myeloid leukemia. We molecularly analyzed the breakpoints of der(1;7)(q10;p10) by quantitative fluorescent in situ hybridization (FISH) analyses using centromeric satellite DNAs ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0031
更新日期:2003-10-01 00:00:00
abstract::Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Bec...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2011-11-370130
更新日期:2012-04-12 00:00:00
abstract::The human CD11a molecule is expressed specifically on lymphocytes, monocyte/macrophages, and neutrophils, in which it mediates important adhesion-related functions. We used 1.7 kb of regulatory sequences upstream from the human CD11a gene transcription start site to drive expression of a modified human CD4 reporter ge...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::Clinical resistance to imatinib mesylate is commonly observed in patients with advanced Philadelphia chromosome- positive (Ph(+)) leukemias. Acquired resistance is typically associated with reactivation of BCR-ABL due to kinase domain mutations or gene amplification, indicating that BCR-ABL remains a viable target for...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1361
更新日期:2002-10-15 00:00:00
abstract::The effects of factor IX concentrate therapy on hemostasis in hemophilia patients were studied by means of the radiometric factor IXa assay, the coupled amidolytic assay for factor VIIa, and coagulant assays for factors II, IX, and X, and antithrombin III. Both activated and unactivated concentrates contained factors ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::We have investigated the clonality of Ph1-negative hemopoietic progenitor cells appearing in long-term marrow cultures established with cells from a mosaic Turner syndrome patient (46,XX/45,X) with Ph1-positive chronic myeloid leukemia (CML). The Ph1-positive clone had been shown previously to have arisen from a cell ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
abstract::The prognostic significance of c-kit receptor expression on leukemic blast cells was determined in 122 children with acute myeloid leukemia (AML) entered onto Childrens Cancer Group protocol 213. Clinical and laboratory characteristics as well as outcome were analyzed according to the percentage of blast cells express...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:
更新日期:1994-08-01 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is a severe renal disease that is associated with defective complement regulation caused by multiple factors. We previously described the deficiency of factor H-related proteins CFHR1 and CFHR3 as predisposing factor for aHUS. Here we identify in an extended cohort of 147 aHUS...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-109876
更新日期:2008-02-01 00:00:00
abstract::The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood-2004-09-3728
更新日期:2005-07-01 00:00:00
abstract::We have investigated the structure of the Ig heavy (IGH) chain locus in 309 cases of acute leukemia. Seventy-one cases of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) were analyzed: in six cases deletion of joining (JH) segments in the presence of cytogenetically normal chromosome 14 was observed. Similar...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Precursor B-cell acute lymphoblastic leukemias (B-ALLs) have been shown to be oligoclonal at the Ig heavy-chain (IgH) gene level in up to 40% of cases by Southern blot hybridization. In contrast, oligoclonality as deduced from diversity of T-cell receptor (TcR)-delta gene rearrangements of the immature types (ie, V de...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-05-15 00:00:00
abstract::In individuals with sickle cell disease, a variable number of irreversibly sickled cells (ISC) is present that may contribute to the pathophysiology of sickle cell anemia. The present study was undertaken to determine the possible role of membrane lipid peroxidation in the genesis of ISC. After 24 hr of simple aerobic...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-02-01 00:00:00
abstract::The Graffi murine leukemia virus induces a large spectrum of leukemias in mice and thus provides a good model to compare the transcriptome of all types of leukemias. We analyzed the gene expression profiles of both T and B leukemias induced by the virus with DNA microarrays. Given that we considered that a 4-fold chan...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-10-311001
更新日期:2011-02-10 00:00:00
abstract::Functional studies on native human dendritic cells (DCs) are hampered by technical difficulties in preparing fresh DCs. Recently, with the help of the monoclonal antibody M-DC8, we succeeded in isolating a major subpopulation of human blood DCs by a one-step immunomagnetic separation procedure. These cells strongly ex...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00
abstract::This study was performed to assess the utility of tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA), for identifying high-risk patients for relapse of acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloSCT)....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-10-880690
更新日期:2019-06-20 00:00:00