Abstract:
:Mixed lineage leukemia (MLL/KMT2A) rearrangements (MLL-r) are one of the most frequent chromosomal aberrations in acute myeloid leukemia. We evaluated the function of Meningioma 1 (MN1), a co-factor of HOXA9 and MEIS1, in human and murine MLL-rearranged leukemia by CRISPR-Cas9 mediated deletion of MN1. MN1 was required for in vivo leukemogenicity of MLL positive murine and human leukemia cells. Loss of MN1 inhibited cell cycle and proliferation, promoted apoptosis and induced differentiation of MLL-rearranged cells. Expression analysis and chromatin immunoprecipitation with sequencing from previously reported data sets demonstrated that MN1 primarily maintains active transcription of HOXA9 and HOXA10, which are critical downstream genes of MLL, and their target genes like BCL2, MCL1 and Survivin. Treatment of MLL-rearranged primary leukemia cells with anti-MN1 siRNA significantly reduced their clonogenic potential in contrast to normal CD34+ hematopoietic progenitor cells, suggesting a therapeutic window for MN1 targeting. In summary, our findings demonstrate that MN1 plays an essential role in MLL fusion leukemias and serve as a therapeutic target in MLL-rearranged acute myeloid leukemia.
journal_name
Haematologicajournal_title
Haematologicaauthors
Sharma A,Jyotsana N,Gabdoulline R,Heckl D,Kuchenbauer F,Slany RK,Ganser A,Heuser Mdoi
10.3324/haematol.2018.211201subject
Has Abstractpub_date
2020-05-01 00:00:00pages
1294-1305issue
5eissn
0390-6078issn
1592-8721pii
haematol.2018.211201journal_volume
105pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract::With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pa...
journal_title:Haematologica
pub_type: 传,历史文章,杂志文章,评审
doi:10.3324/haematol.2015.139337
更新日期:2016-05-01 00:00:00
abstract::MicroRNA-34b down-regulation in acute myeloid leukemia was previously shown to induce CREB overexpression, thereby causing leukemia proliferation in vitro and in vivo. The role of microRNA-34b and CREB in patients with myeloid malignancies has never been evaluated. We examined microRNA-34b expression and the methylati...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2012.070664
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:Immunoglobulin gene somatic hypermutation is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas, including chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. DESIGN AND METHODS:With the aim of identifying surro...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12999
更新日期:2008-08-01 00:00:00
abstract::Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2015.141622
更新日期:2016-07-01 00:00:00
abstract::There is emerging consensus that a pro-inflammatory condition contributes to the vaso-occlusive complications of sickle cell disease (SCD). We evaluated the potential value of inflammatory mediators as early markers of severity of painful vaso-occlusive crises (VOC) in SCD. We assayed the plasma levels of cytokines, s...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Diffuse large B-cell lymphomas (DLBCL) have a variable outcome, and powerful methods of prognostication are needed in order to choose the best treatment for each patient. Immunophenotypic classification of the tumor as germinal center (GC) or non-germinal center-like (nGC) and early response e...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10895
更新日期:2007-06-01 00:00:00
abstract::Renewing interest in cancer immunotherapy reflects the excellent results that have been obtained in animal models and the promising results in early clinical trails with dendritic cell (DC) based approaches. The central role that DCs play in the initiation of an immune response raises the possibility of using them to ...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2000-02-01 00:00:00
abstract::Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3 mg/m(2)...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.3324/haematol.2016.141937
更新日期:2016-06-01 00:00:00
abstract::The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed a...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2014.116269
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:beta-thalassemia is one of the most common genetic diseases in the world and requires extensive therapy. Lentiviral-mediated gene therapy has been successfully exploited in the treatment of beta-thalassemia and showed promise in clinical application. Using a human beta-globin transgenic mouse line in a beta-...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12010
更新日期:2008-03-01 00:00:00
abstract::Pediatric thromboembolism (≤18 years) is very rare (0.07-0.14/10,000/year) but may be more prevalent in children with severe thrombophilia (protein C, protein S or antithrombin deficiency). The aim of this study was to define the prevalence and clinical characteristics of pediatric thrombosis in subjects with inherite...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.210666
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:The increasing application of multi-color flow cytometry assays for staging and follow-up in mantle cell lymphoma necessitates that the specificity and sensitivity of this technique are evaluated. Data from prospective clinical trials comparing the clinical applicability of flow cytometry to routine diagnost...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.3324/haematol.11267
更新日期:2008-04-01 00:00:00
abstract::Reduced intensity conditioning followed by allogeneic SCT (RIC-SCT) has recently emerged as promising new salvage option for children suffering from Langerhans cell histiocytosis (LCH) with risk organ involvement and failure to conventional therapy. We report on the posttransplant course of female toddler with high-ri...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10993
更新日期:2007-01-01 00:00:00
abstract::Most DNA methylation studies in classic Philadelphia-negative myeloproliferative neoplasms have been performed on a gene-by-gene basis. Therefore, a more comprehensive methylation profiling is needed to study the implications of this epigenetic marker in myeloproliferative neoplasms. Here, we have analyzed 71 chronic ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2013.084160
更新日期:2013-09-01 00:00:00
abstract::To our knowledge, there is little information about functional thrombin activatable fibrinolysis inhibitor (TAFI) levels and the risk of acute coronary artery disease (CAD). We investigated the risk of acute CAD related to plasma levels of functional TAFI. We found that functional TAFI levels in plasma (above 126%), i...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:It has been shown that fludarabine (FLU) is superior to conventional treatment in B-CLL for rate and quality of response, leading to CR even at the molecular level. In this paper we report our preliminary results with this drug in B-CLL patients. METHODS AND PATIENTS:Twenty-seven B-CLL patients (16 refracto...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN. However, it is not clear whether NOTCH1 mutations associate with decreased PTEN expression in primary T-ALL. Here, we compared patients with or wi...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.011999
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND:Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studie...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3324/haematol.2011.042937
更新日期:2011-12-01 00:00:00
abstract::Circulating stem cells (CSC) are well documented in animals and humans. Though their function in normal conditions remains obscure, autologous CSC seem capable of restoring hemopoiesis after myeloablative treatment. With cell separators CSC may be harvested in adequate number, and collection may be further improved gi...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:1990-11-01 00:00:00
abstract::Twenty-five adult patients with resistant or early relapsing Hodgkin's disease have been treated with CAV combination chemotherapy (CCNU, melphalan and etoposide). All patients had previously received both MOPP and ABVD regimens (23 patients as primary therapy and two as first salvage). High-energy radiotherapy had be...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1990-07-01 00:00:00
abstract::The success story of hemophilia care first began in the 1970s, when the availability of plasma-derived concentrates of coagulation factor VIII (FVIII) and factor IX (FIX) provided efficacious treatment of bleeding in patients with hemophilia A and B. This positive scenario was consolidated in terms of greater safety a...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.232132
更新日期:2020-03-01 00:00:00
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:
更新日期:1997-05-01 00:00:00
abstract::To investigate the role of oral contraceptives and their interaction with thrombophilia in ischemic stroke, a case-control study on women with a first ischemic stroke when younger than 45 years was carried out. Oral contraceptives doubled the risk of ischemic stroke in the first 6-18 months of use and hyperhomocystein...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The efficacy of antithymocyte globulin (ATG) in the treatment of graft-versus-host disease (GvHD) is controversial. In the present study we report on the use of low dose ATG (thymoglobuline, Sangstat) and steroids in 28 patients with moderate to severe acute GvHD. DESIGN AND METHODS:Fifteen p...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2002-09-01 00:00:00
abstract::Macaques are emerging as a critical animal model in transfusion medicine, because of their evolutionary similarity to humans and perceived utility in discovery and translational science. However, little is known about the metabolism of Rhesus macaque red blood cells (RBC) and how this compares to human RBC metabolism ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.229930
更新日期:2020-08-01 00:00:00
abstract::It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10683
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:The myeloproliferative neoplasms, essential thrombocytosis, polycythemia vera and primary myelofibrosis, share the same acquired genetic lesion, but the concept of JAK2 V617F serving as the sole lesion responsible for these neoplasms is under question, and there has been interest in identifying additional mu...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.045591
更新日期:2011-10-01 00:00:00
abstract:PURPOSE:Various experiences show no substantial differences between children and adults in the treatment of Hodgkin's disease. In consideration of some peculiar characteristics of these cases which might influence the therapeutical choice, particularly regarding long-term survival and therapeutical complications, we re...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Patients with chronic renal failure show signs of accelerated atherosclerosis and high cardiovascular morbidity and mortality. Recent investigations indicate that uremia is associated with endothelial dysfunction and a microinflammatory state. We assessed changes in the expression of adhesion ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::Chronic autoimmune or pathogen-induced immune reactions resulting in lymphoid neogenesis are associated with development of malignant lymphomas, mostly extranodal marginal zone B-cell lymphomas (MZBCLs). In this review we address (i) chemokines and adhesion molecules involved in lymphoid neogenesis; (ii) the autoimmun...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.2009.005983
更新日期:2009-08-01 00:00:00