Abstract:
BACKGROUND:Acute myeloid leukemia (AML) represents a heterogeneous disorder with recurrent chromosomal alterations and molecular abnormalities. Among AML with normal karyotype (NK-AML) FLT3 activating mutation, internal tandem duplication (FLT3-ITD), is present in about 30% of patients, conferring unfavorable outcome. Our previous data demonstrated specific up-regulation of miR-155 in FLT3-ITD+ AML. miR-155 is known to be directly implicated in normal hematopoiesis and in some pathologies such as myeloid hyperplasia and acute lymphoblastic leukemia. METHODS AND RESULTS:To investigate about the potential influence of miR-155 de-regulation in FLT3-mutated AML we generated a transcription factors regulatory network and combined this with data from multiple sources that predict miR-155 interactions. From these analyses, we derived a sub-network, called "miR-155 module" that describes functional relationship among miR-155 and transcription factors in FLT3-mutated AML. We found that "miR-155 module" is characterized by the presence of six transcription factors as central hubs: four miR-155 regulators (JUN, RUNX1, FOSb, JUNB) and two targets of miR-155 (SPI1, CEBPB) all known to be "master" genes of myelopoiesis. We found, in FLT3-mutated AML, a significant down-regulation of miR-155 target genes CEBPB and SPI1 and up-regulation of miR-155 regulator genes JUN and RUNX1. We also showed that PKC412-related FLT3 inhibition, in MV4-11 cell line, causes down-regulation of miR-155 and increased level of mRNA and protein of miR-155 target SPI1. We showed in experiments of miR-155 mimic in K562 cell line, a high increase of miR-155 and an inverse correlation with the mRNA levels of its targets SPI1 and CEBPB. Moreover silencing of miR-155 in primary AMLs causes mRNA up-regulation of its target SPI1 and CEBPB. CONCLUSION:Our results suggest that activating mutation of FLT3 in AML can lead, through the induction of JUN, to an increased expression of miR-155, which then causes down-regulation of SPI1 and CEBPB and consequently may causes block of myeloid differentiation.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Salemi D,Cammarata G,Agueli C,Augugliaro L,Corrado C,Bica MG,Raimondo S,Marfia A,Randazzo V,Dragotto P,Di Raimondo F,Alessandro R,Fabbiano F,Santoro Adoi
10.1016/j.leukres.2015.04.017subject
Has Abstractpub_date
2015-08-01 00:00:00pages
883-96issue
8eissn
0145-2126issn
1873-5835pii
S0145-2126(15)00128-9journal_volume
39pub_type
杂志文章abstract::DNAs from chronic granulocytic leukaemia (CGL) and chronic myelomonocytic leukaemia (CMML) were assayed for transforming genes by transfection into NIH 3T3 cells. Foci DNA was tagged with a geneticin-resistance cosmid, then followed through a drug selection and tumorigenicity assay. Activated Ha-ras genes, with point ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(88)90033-1
更新日期:1988-01-01 00:00:00
abstract::Screening for loss of heterozygosity (LOH) of the panel of 18 highly polymorphic microsatellite markers, especially from the region 11p15, was carried out on 154 samples from 26 patients with acute myeloid leukemia and eight with myelodysplastic syndromes (MDS). LOH was detected at the majority (72%) of the loci teste...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(00)00086-2
更新日期:2001-01-01 00:00:00
abstract::The Philadelphia (Ph1) chromosome is a specific structural abnormality in which the abl oncogene is activated due to the formation of the novel chimeric gene, bcr/abl. To investigate the clinicopathological role of bcr/abl in Ph1-positive chronic myelogenous leukaemia (CML), we studied the clonal origin of haematopoie...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90139-x
更新日期:1992-01-01 00:00:00
abstract::Human promyelocytic leukemia cells (HL-60) mature into functional granulocytes in response to in vitro treatment with several classes of chemical agents. Compounds that increase intracellular adenosine 3':5' -cyclic monophosphate induce a modified program of maturation in which the cells demonstrate functional propert...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(85)90311-x
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Therapy strategies for myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) vary considerably. OBJECTIVE:To review the treatment of Brazilian children who were diagnosed with MDS or JMML in the past decade and reported to the Brazilian Cooperative Group on Pediatric Myelodysplastic Sy...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2004.01.008
更新日期:2004-09-01 00:00:00
abstract::Reversal of drug resistance is of pivotal importance in order to improve the results of chemotherapy. Monitoring of such reversal is necessary in order to analyze the results of clinical trials. Nonetheless, the leukemia cell population to eradicate is the leukemia initiating cells characterized by a CD34+CD38- phenot...
journal_title:Leukemia research
pub_type: 评论,社论
doi:10.1016/j.leukres.2008.09.022
更新日期:2009-06-01 00:00:00
abstract::Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have recently shown a sig...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.08.018
更新日期:2010-05-01 00:00:00
abstract::FcRIII (CD16) expression on neutrophils from 17 patients with chronic myeloid leukemia (CML) was studied by flow cytometry using monoclonal antibodies. A variable proportion of CD16-negative neutrophils were found both in CML patients in chronic phase (3 out of 8 patients) and in CML patients in hematological remissio...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90120-v
更新日期:1992-12-01 00:00:00
abstract::Activating mutations of the c-kit gene are frequently found in CBF (core binding factor) leukemias. We evaluated the effect of tyrosine kinase inhibitor dasatinib in leukemic cell lines bearing or not c-kit mutations. Our data demonstrate that in the AML Kasumi-1 cell line, bearing the N822K c-kit mutation, dasatinib ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2012.10.011
更新日期:2013-02-01 00:00:00
abstract::HSP90 is a multi-client chaperone involved in regulating a large array of cellular processes and is commonly overexpressed in many different cancer types including hematological malignancies. Inhibition of HSP90 holds promise for targeting multiple molecular abnormalities and is therefore an attractive target for hete...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2015.03.016
更新日期:2015-06-01 00:00:00
abstract::A novel bone biopsy technique was used to generate a robust stromal cell system to study how stroma modulates CLL B-cell apoptosis and how the leukemic cell-stromal interaction influences secretion of vascular factors. Marrow stromal elements (MSE) rescued CLL B-cells from both spontaneous and drug induced apoptosis, ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.11.024
更新日期:2007-07-01 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous disease. Until recently, treatment for patients with AML was limited to induction chemotherapy with cytarabine and anthracycline or hypomethylating agents, and, in some instances, allogeneic hematopoietic stem cell transplant. With the recent approval of new therapies-i....
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2018.09.001
更新日期:2018-10-01 00:00:00
abstract::Nitric oxide (NO) has been shown to be cytotoxic for normal and transformed cell lines. One of the intracellular targets for NO action is glutathione (GSH). GSH determinates cellular redox potential and modulates several biological events. During oxidative and nitrosative stress, glutathione system imbalance is associ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.06.021
更新日期:2006-02-01 00:00:00
abstract::Delta retrovirus-mediated leukemogenesis is dependent on the oncogenic potential of Tax. It is not clear, however, whether Tax-specific immune responses play a role in leukemia onset and progression. Using the BLV-associated leukemia model in sheep, we found that Tax-specific cytotoxic responses induced by DNA immuniz...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.06.003
更新日期:2010-12-01 00:00:00
abstract::A single somatic mutation, V617F, in the pseudokinase domain of the Jak2 is the primary cause of many chronic myeloproliferative diseases. As valine 617 of Jak2 is conserved as valine 678 of Tyk2, we examined the effect of a homologous mutation in Tyk2 (V678F Tyk2) on cell growth. V678F Tyk2 augmented the transcriptio...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.08.018
更新日期:2007-08-01 00:00:00
abstract::Topotecan has demonstrable activity in high-risk MDS and CMMoL. However, the significant toxicity of topotecan administered at a dose of 2mg/m2 i.v. daily for 5 days as a continuous infusion limits its use in older patients. Therefore, we studied topotecan 1.5mg/m2 per day i.v. over 2 h for three consecutive days in 2...
journal_title:Leukemia research
pub_type: 临床试验,杂志文章
doi:10.1016/s0145-2126(03)00181-4
更新日期:2004-01-01 00:00:00
abstract::The tumor microenvironment (TME) is critical to the longevity of tumor B cells in chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs) and the cytokines they produce including IL-6 are important components of the TME in CLL. We found BMMSCs supported the survival of CLL cells in vitro throug...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2018.01.006
更新日期:2018-03-01 00:00:00
abstract::We describe the properties of three monoclonal antibodies (McAbs) (21H73, 37G7 and 49C12) against K562 cell surface antigens correlated with differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Each of the McAbs immunoprecipitated K562 cell surface antigen with molecular weight (MW) of approximately...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(91)90121-9
更新日期:1991-01-01 00:00:00
abstract::K-562 is described as a pluripotent leukemic cell line which expresses a diversity of hematopoietic cell differentiation antigens. With the use of monoclonal antibodies (MoAb), we show that the expression of these antigens is either "modulated", i.e. they are not expressed in early logarithmic growth but are expressed...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(87)90181-0
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytome...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2005.02.015
更新日期:2005-10-01 00:00:00
abstract::Interleukin-8 (IL-8) mRNA was rapidly, but not permanently, induced at high levels by phorbol-12myristate-13acetate (PMA) in HL60 cells. Ongoing protein synthase does not seem to be required for the initial induction of IL-8 gene expression. However, the rate of transient induction kinetics was modulated by cyclohexim...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)00151-y
更新日期:1995-07-01 00:00:00
abstract::Aggressive chemotherapy of myelodysplastic syndromes is rarely feasible because these disorders predominantly occur in elderly patients who often have concurrent illnesses. Alternative treatment modalities must therefore be evaluated. This review summarizes the results that have been obtained with low-dose chemotherap...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/0145-2126(92)90058-f
更新日期:1992-01-01 00:00:00
abstract::This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cul...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90066-0
更新日期:1989-01-01 00:00:00
abstract::This study aimed at optimizing the conditions for flow cytometric detection of myeloperoxidase (MPO), cytoplasmic CD3 (cCD3), and cytoplasmic CD22 (cCD22), which seem to be more reliable lineage-associated markers in acute leukemia than surface antigens. Fixation methods employing saponin as detergent resulted in accu...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90102-q
更新日期:1993-05-01 00:00:00
abstract::The hotspot c.7541_7542delCT NOTCH1 mutation has been proven to have a negative clinical impact in chronic lymphocytic leukemia (CLL). However, an optimal method for its detection has not yet been specified. The aim of our study was to examine the presence of the NOTCH1 mutation in CLL using three commonly used molecu...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2017.08.001
更新日期:2017-09-01 00:00:00
abstract::During monocyte-macrophage differentiation of HL-60 cells by 12-O-tetradecanoyl phorbol 13-acetate, the intracellular globular(G)-actin and polymerized(F)-actin increased 3-fold and 1.7-fold, respectively. Time course studies showed that these changes of actin levels were nearly coincident with the development of macr...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90121-5
更新日期:1989-01-01 00:00:00
abstract::In a patient affected with chronic lymphocytic leukemia with lymphocyte surface mu and kappa determinants and vacuolated bone marrow plasma cells, the serum contained polymers of a truncated mu chain and normal-sized kappa chains. These light chains were present as monomers and covalent dimers in studies performed und...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90129-9
更新日期:1993-06-01 00:00:00
abstract::Migration of eosinophil (Eo) into tissues is a hallmark of chronic eosinophilic leukaemia (CEL), but the exact mechanism involved in cell migration is unknown. We report on a patient with CEL who presented high expressions of VLA-4, LFA-1 and Mac-1 integrins on the Eo surface, increased chemotaxis of Eo to eotaxin, de...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.07.025
更新日期:2007-05-01 00:00:00
abstract::Magnetic resonance provides a non-invasive tool for monitoring normal and leukemic bone marrow. Measurements of the T1 relaxation times are elevated in acute myelogenous leukemia. However, interpatient variability diminishes the usefulness of MR measurements for diagnosing leukemia. In following the time course of ind...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(88)90034-3
更新日期:1988-01-01 00:00:00
abstract::The myelodysplastic syndrome is a paradigm of human preleukaemia. Normal haemopoiesis is progressively displaced by an abnormal clone derived from a mutated stem cell. The initial mutation is unknown but its occurrence may be related to the overall load of random mutations which are a consequence of both intrinsic DNA...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/0145-2126(92)90099-s
更新日期:1992-01-01 00:00:00