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 methylation status of its promoter in cells from patients diagnosed with myeloid malignancies. We used gene expression profiling to identify signatures of myeloid transformation. We established that microRNA-34b has suppressor ability and that CREB has oncogenic potential in primary bone marrow cell cultures and in vivo. MicroRNA-34b was found to be up-regulated in pediatric patients with juvenile myelomonocytic leukemia (n=17) and myelodysplastic syndromes (n=28), but was down-regulated in acute myeloid leukemia patients at diagnosis (n=112). Our results showed that hypermethylation of the microRNA-34b promoter occurred in 66% of cases of acute myeloid leukemia explaining the low microRNA-34b levels and CREB overexpression, whereas preleukemic myelodysplastic syndromes and juvenile myelomonocytic leukemia were not associated with hypermethylation or CREB overexpression. In paired samples taken from the same patients when they had myelodysplastic syndrome and again during the subsequent acute myeloid leukemia, we confirmed microRNA-34b promoter hypermethylation at leukemia onset, with 103 CREB target genes differentially expressed between the two disease stages. This subset of CREB targets was confirmed to associate with high-risk myelodysplastic syndromes in a separate cohort of patients (n=20). Seventy-eight of these 103 CREB targets were also differentially expressed between healthy samples (n=11) and de novo acute myeloid leukemia (n=72). Further, low microRNA-34b and high CREB expression levels induced aberrant myelopoiesis through CREB-dependent pathways in vitro and in vivo. In conclusion, we suggest that microRNA-34b controls CREB expression and contributes to myeloid transformation from both healthy bone marrow and myelodysplastic syndromes. We identified a subset of CREB target genes that represents a novel transcriptional network that may control myeloid transformation.
journal_name
Haematologicajournal_title
Haematologicaauthors
Pigazzi M,Manara E,Bresolin S,Tregnago C,Beghin A,Baron E,Giarin E,Cho EC,Masetti R,Rao DS,Sakamoto KM,Basso Gdoi
10.3324/haematol.2012.070664subject
Has Abstractpub_date
2013-04-01 00:00:00pages
602-10issue
4eissn
0390-6078issn
1592-8721pii
haematol.2012.070664journal_volume
98pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract::Germline RUNX1 mutations lead to thrombocytopenia and platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia (AML). Multiple aspects of platelet function are impaired in these patients, associated with altered expression of genes regulated by RUNX1 We aimed to identify RUN...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.188904
更新日期:2019-06-01 00:00:00
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
更新日期:2013-07-01 00:00:00
abstract::The transferability of the T2* technique for measurement of tissue iron between magnetic resonance (MR) scanners is unknown. Heart and liver multi-breath-hold T2* sequences were installed on MR scanners at six different sites. T2* was assessed locally in five or more patients with thalassemia major (n=39), and subject...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:
更新日期:2006-10-01 00:00:00
abstract::Leukemia stem cells contribute to drug-resistance and relapse in chronic myeloid leukemia (CML) and BCR-ABL1 inhibitor monotherapy fails to eliminate these cells, thereby necessitating alternate therapeutic strategies for patients CML. The peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone downr...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.194910
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Chimeric oncogenes encoding constitutively active protein tyrosine kinases are associated with chronic myeloid neoplasms. TEL-PDGFRbeta (TPbeta, also called ETV6-PDGFRB) is a hybrid protein produced by the t(5;12) translocation, FIP1L1-PDGFRalpha (FPalpha) results from a deletion on chromosome 4q12 and ZNF19...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2008.001149
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:We investigated whether cytogenetic findings (CG) on day 21 (D21) of the first course of chemotherapy predicted subsequent outcome in patients who presented with CG abnormalities. DESIGN AND METHODS:D21 CG analysis was performed in 197 patients. RESULTS:Nineteen percent of the patients had e...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:Usefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.016824
更新日期:2010-08-01 00:00:00
abstract::Children with immune thrombocytopenia for ≥6 months completing a romiplostim study received weekly subcutaneous romiplostim (1-10 μg/kg targeting platelet counts of 50-200×109/L) in this extension to examine romiplostim's long-term safety and efficacy. Sixty-five children received romiplostim for a median of 2.6 years...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.202283
更新日期:2019-11-01 00:00:00
abstract::As of 1999, the German registry of immune tolerance treatment in hemophilia has received reports on 146 patients who have undergone this therapy from 25 hemophilia centers. In 16 of the reported patients treatment is ongoing. Therapy has been completed in 126 patients of all groups with hemophilia A; most of them are ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract::We report a family with type I and type III protein S (PS) deficiency, which showed to be phenotypic variants of the same genetic disease. Direct sequencing analysis of the PROS1 gene was performed to establish the genotype. The ratio of protein C antigen and total PS antigen levels (protein C/S ratio) was used to cla...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-08-01 00:00:00
abstract::Lenalidomide is a very active drug in myelodysplastic syndrome with del (5q). We report such a patient treated with this drug who developed unusual complex cytogenetic abnormalities, which were elucidated by multi-FISH and FISH analysis as jumping translocations involving the long arm of chromosome 5, that resulted in...
journal_title:Haematologica
pub_type: 信件
doi:10.3324/haematol.11917
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Polycythemia vera is a clonal hematopoietic stem cell disorder in which the JAK2 V617F mutation is observed in >95% of patients, but an as yet unidentified process appears to initiate the clonal expansion of hematopoiesis. Because microRNA regulate hematopoietic differentiation, we hypothesized that dysregul...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12706
更新日期:2008-07-01 00:00:00
abstract::Normal hematopoiesis can be disrupted by the leukemic bone marrow microenvironment, which leads to cytopenia-associated symptoms including anemia, hemorrhage and infection. Thrombocytopenia is a major and sometimes fatal complication in patients with acute leukemia. However, the mechanisms underlying defective thrombo...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.214593
更新日期:2019-10-01 00:00:00
abstract::Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing CNS recurrence is unclear and remains controversial. No systematic review analysing the evidence for stand-alone intrathecal prophylaxis has been perfor...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.229948
更新日期:2020-07-01 00:00:00
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
更新日期:2012-04-01 00:00:00
abstract::A new method, combining seminested polymerase chain reaction (PCR) with heteroduplex analysis, was utilized to detect follicular lymphoma (FL) cells in peripheral blood. The method, based on the detection of IgH rearrangements in DNA, detected the presence of monoclonal B cells in FL patients with a high frequency. ...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2005-02-01 00:00:00
abstract::All hematopoietic cells that develop in the bone marrow must cross the endothelial barrier to enter the blood circulation. Blood platelets, however, are released by bigger protrusions of huge progenitor cells, named megakaryocytes, and enter the blood stream as so-called proplatelets before fragmenting into mature pla...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.202010
更新日期:2020-04-01 00:00:00
abstract::We evaluate the long-term results of a prospective clinical study enrolling more than 100 adult patients with Burkitt lymphoma/leukemia. Depending on extent of disease, treatment consisted of six to eight rituximab infusions and four to six courses of intensive chemotherapy (attenuated in patients aged >55 years) with...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3324/haematol.2013.086827
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Patients with hematologic malignancies can be successfully treated with donor lymphocyte infusion after HLA-matched allogeneic hematopoietic stem cell transplantation. The effect of donor lymphocyte infusion is mediated by donor T cells recognizing minor histocompatibility antigens. T cells recognizing hemat...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.049478
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Subgroups of T-cell acute lymphoblastic leukemia (T-ALL), defined according to recurrent cytogenetic aberrations, may have different prognoses. The aim of this study was to determine the prognostic relevance of molecular-cytogenetic abnormalities in pediatric patients using quantitative real-t...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Interleukin-17A is the signature cytokine of the Th17 subset and drives inflammatory pathology, but its relevance to autoantibody-mediated diseases is unclear. Th1 cells secreting interferon-γ have been implicated in autoimmune hemolytic anemia, so the aim was to determine which cytokine is more closely asso...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.060822
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND:31D8 monoclonal antibody (mAb) has been shown to bind heterogeneously to human neutrophils, identifying subsets of cells which differ in their functional response to chemotactic stimuli. In this study we used 31D8 mAb to determine whether differences in neutrophil subpopulations might explain the long-lastin...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions. Using data from patients enrolled in Total Therapy 3...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2012.066555
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Research on prognostically relevant immunohistochemical markers in diffuse large B-cell lymphomas has mostly been performed on retrospectively collected clinical data. This is also true for immunohistochemical classifiers that are thought to reflect the cell-of-origin subclassification of gene expression stu...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.008862
更新日期:2009-11-01 00:00:00
abstract::Recent advances in unrelated cord blood transplantation have increased chances and options available in allogeneic stem cell transplantation. The effect of HLA disparity on outcomes after cord blood transplantation was studied recently in mainly pediatric populations. Results showed that HLA matching in combination wi...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2012.076042
更新日期:2013-05-01 00:00:00
abstract::Left ventricular (LV) failure is the main cause of death in thalassemia. Iron overload in patients with thalassemia leads to the formation of oxygen free radicals. Of the various apolipoprotein E (apoE) alleles, apoE4 is the least efficient in conditions of oxidative stress in comparison with apoE2 and apoE3. Our resu...
journal_title:Haematologica
pub_type: 信件
doi:10.3324/haematol.10708
更新日期:2007-02-01 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::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:Mesenchymal stem cells (MSC) are progenitor cells that are capable of differentiating into mesenchymal tissues. Fetal and adult MSC have similar morphology but differ in proliferative, differentiating and immunosuppressive properties. Further exploring their differences could help in choosing ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2005-08-01 00:00:00
abstract::HTLV-1 infections and their associated diseases are very rare in Italy, as well as in most parts of Europe, occurring prevalently in subjects related to endemic areas. The HTLV-1-associated leukemia/lymphoma, ATLL, is a very aggressive T-cell non-Hodgkin's lymphoma which can be difficult to recognize in non-endemic ar...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00