Abstract:
:Aberrant promoter methylation may contribute to the hematopoietic disturbances in myelodysplastic syndromes (MDS). To explore a possible mechanism, we therefore analyzed expression of DNA methyltransferase (DNMT) subtypes kinetics and aberrant promoter methylation of key regulatory genes during MDS hematopoiesis. An in vitro model of MDS lineage-specific hematopoiesis was generated by culturing CD34+ cells from healthy donors (n=7) and MDS patients (low-risk: RA/n=6, RARS/n=3; high-risk: RAEB/n=4, RAEB-T/n=2) with EPO, TPO and GCSF. Promoter methylation analysis of key genes involved in the control of apoptosis (p73, survivin, DAPK), DNA-repair (hMLH1), differentiation (RARb, WT1) and cell cycle control (p14, p15, p16, CHK2) was performed by methylation specific PCR of bisulfite-treated genomic DNA. Expression of DNMT1, DNMT3a and DNMT3b was analyzed and correlated with gene promoter methylation for each lineage at different time points. DNMT expression (all isoforms) was increased during thrombopoiesis whereas elevated DNMT1 level were seen during erythropoiesis. Associations between aberrant promoter methylation and DNMT expression were found in high-risk MDS for all lineages and during erythropoiesis. Hypermethylation of p15, p16, p73, survivin, CHK2, RARb and DAPK were associated with elevated DNMT isoform expression. No general overexpression of DNMT subtype was detected during MDS hematopoiesis. However a negative association of DNMT3a and 3b expression with MDS disease risk (IPSS) could be observed. Our data indicate that all mammalian DNMT isoforms may be involved in the aberrantly methylated phenotype in MDS but seem also to be essential for the differentiation of normal hematopoietic stem cells. In particular elevated DNMT1 expression may in particular contribute to ineffective erythropoiesis in MDS.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Hopfer O,Komor M,Koehler IS,Freitag C,Schulze M,Hoelzer D,Thiel E,Hofmann WKdoi
10.1016/j.leukres.2008.08.014subject
Has Abstractpub_date
2009-03-01 00:00:00pages
434-42issue
3eissn
0145-2126issn
1873-5835pii
S0145-2126(08)00370-6journal_volume
33pub_type
杂志文章abstract::Cell line PER-423 was derived from the cells of a patient with an immature acute T-lymphoblastic leukaemia and the growth of this human cell line is strictly dependent on interleukin-2 (IL-2). PER-423 cells express the p75 (beta) subunit of the IL-2 receptor (IL-2R beta), while the p55 chain (IL-2R alpha) is not detec...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90141-7
更新日期:1993-01-01 00:00:00
abstract::p23 is a heat shock protein 90 (Hsp90) cochaperone that plays a significant role in estrogen receptor (ER) alpha signal transduction and telomerase activity; it is up-regulated in several cancers. Recent studies have found that high level of p23 may promote tumor progression and poor prognosis in breast cancer patient...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2012.05.003
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivit...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2018.06.014
更新日期:2018-08-01 00:00:00
abstract::Osteogenic growth peptide (OGP) is a peptide exerting regulatory effects on the bone and on bone marrow. The carboxy-terminal pentapeptide (OGP10-14) is the biologically active portion of OGP. We evaluated OGP10-14 hematopoietic activity performing colony-forming tests on human stem cells derived by bone marrow, perip...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(02)00008-5
更新日期:2002-09-01 00:00:00
abstract::The usefulness of a new method to detect B-cell monoclonality named VR, which is a combination of the digestion with restriction enzymes and vectorette PCR, in aspiration biopsy-nucleic acid diagnosis (ABND) of thyroid malignant lymphoma was investigated. ABND was performed in 12 patients in whom malignant lymphoma wa...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.03.019
更新日期:2008-01-01 00:00:00
abstract::240 patients with MDS studied cytogenetically at diagnosis between 1981 and 1990 were followed until death or until April 1992 to evaluate the prognostic significance of FAB classification, age and karyotype. 61 patients (25.4%) subsequently transformed into AML and 176 (73.3%) died during the follow-up period. Patien...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)00131-s
更新日期:1995-05-01 00:00:00
abstract::To determine the clinical significance of the T helper 1(Th1)/T helper 2 (Th2) ratio in multiple myeloma, the intracellular IFN-gamma and IL-4 were analyzed by flow cytometry in 56 patients with multiple myeloma. The mean Th1/Th2 ratio of cases in the initial diagnosis phase and the refractory phase were higher than t...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.06.003
更新日期:2005-02-01 00:00:00
abstract::We present our first experiences with determination of minimal residual disease (MRD) based on patient specific Flt3-ITD (internal tandem duplication) mutations. We analysed MRD status of 11 AML patients in a retrospective investigation and its potential impact on the follow up of these patients. In five out of six pa...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.12.001
更新日期:2005-07-01 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 t(14;18) translocation is closely associated with the follicular lymphoma but is also seen in diffuse B cell lymphomas with a previous history of a follicular lymphoma as well as de novo diffuse lymphomas. Estimation of the frequency of t(14;18) in follicular lymphoma vary widely from 33 to 89%. Furthermore, no exte...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(00)00009-6
更新日期:2000-06-01 00:00:00
abstract::We studied 98 female patients in remission (2-240 months) from childhood ALL to determine the clonality status of their hematopoiesis. Thirty-one (31.6%) were heterozygous at the PGK locus for the BstX1 endonuclease restriction site, permitting X-linked clonality assays to be performed. Two patients were in relapse at...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)90121-x
更新日期:1994-02-01 00:00:00
abstract::Normal human peripheral blood polymorphonuclear leukocytes (PMNs) and cells from a human acute promyelocytic leukemia line (HL-60) were tested for cytotoxic potential against two human glioma and one normal fibroblast line. Both the PMNs and HL-60 exhibited significant cytotoxicity against the tumor targets while spar...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(84)90101-2
更新日期:1984-01-01 00:00:00
abstract::The amplified myeloma centrosome has been identified as a therapeutic target. The present study explored the expression and prognostic significance of the centrosome-associated protein PLK1 in myeloma and the effect of BI 2536, a potent and selective inhibitor of PLK1, on myeloma cells. High plasma cell expression of ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2011.07.016
更新日期:2011-12-01 00:00:00
abstract::In a previous study we reported that a new anthracycline derivative (moflomycin) exhibited a higher antileukemic activity compared to other anthracyclines, such as daunorubicin and doxorubicin. To explain the superior antileukemic effect of moflomycin and to disclose a possible structure-activity relationship, we inve...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(95)00155-7
更新日期:1996-02-01 00:00:00
abstract::The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic malignancies characterized by ineffective hematopoiesis, progressive bone marrow (BM) failure, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia (AML). The BM microenvironment in MDS plays ...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2015.06.017
更新日期:2015-10-01 00:00:00
abstract::The involvement of histone lysine methyltransferases (HMT) in carcinogenesis is not well understood. Here, we describe a dose-dependent growth and survival inhibitory effects of BIX-01294, a specific inhibitor of euchromatic HMT2, in promyelocytic leukemia HL-60 and NB4 cells. BIX-01294 combined with all-trans retinoi...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2014.04.003
更新日期:2014-07-01 00:00:00
abstract::Immunophenotypic classification of the acute leukemias (AcL) is of well documented value in those of lymphoid or uncertain origin and of increasing importance in those of nonlymphoid origin. Most of these studies have been performed on viable cell suspensions. To study the efficacy of a simpler immunohistochemical app...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(87)90080-4
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:Chronic Myeloid Leukemia (CML) is characterized by the overproduction of BCR-ABL, a tyrosine kinase with constitutive activity, in which the majority of CML patients have e13a2 or e14a2 transcripts. Reckoned the possible associations between the hematologic and molecular features of the disease, a profound u...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2021.106512
更新日期:2021-01-19 00:00:00
abstract::Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.12.016
更新日期:2009-09-01 00:00:00
abstract::microRNA profiling of acute myeloid leukemia patient samples identified miR-125a as being decreased. Current literature has investigated miR-125a's role in normal hematopoiesis but not within acute myeloid leukemia. Analysis of the upstream region of miR-125a identified several CpG islands. Both precursor and mature m...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2013.12.021
更新日期:2014-03-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) may be underreported in cancer registries such as the Netherlands Cancer Registry (NCR). Analysis of Dutch medical claims can complement NCR data on MDS and CMML. We analyzed data on 3681 MDS patients and 235 CMML patients aged ≥18 years with i...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2014.11.025
更新日期:2015-02-01 00:00:00
abstract::Endonucleases capable of producing internucleosomal DNA cleavage are one of the key enzymes in apoptosis. We examined endonuclease activities contained in nuclei of CD34+ and erythroid cells in the bone marrow (BM) from 12 patients with the myelodysplastic syndromes. The levels of Mg(2+)-dependent and acidic endonucle...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(97)00041-6
更新日期:1997-08-01 00:00:00
abstract::We wish to demonstrate new evidence for the in vivo production of interleukin-3 (IL-3). Syngeneic murine splenocytes were transplanted into lethally irradiated mice. The spleen cells in these transplant mice spontaneously produced IL-3 in cultures, and IL-3-like activity was detected in the serum. Chronological change...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90138-0
更新日期:1989-01-01 00:00:00
abstract::Exogenous expression of the transcription factor Scl (Tal1) in WEHI-3B D+ myelomonocytic leukemia cells interferes with their capacity to respond to all-trans retinoic acid (ATRA) induced differentiation; combination of ATRA with LiCl, however, circumvents the inhibition of differentiation produced by Scl. To gain inf...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.03.017
更新日期:2004-11-01 00:00:00
abstract::In order to investigate the clinical significance of IgG subclass levels in adult patients treated for acute lymphocytic (ALL) or myelogenous leukemias (AML), patients were tested before and in regular intervals during and after chemotherapy. Ten patients treated for acute lymphocytic leukemia had normal total IgG and...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90128-t
更新日期:1992-01-01 00:00:00
abstract::Bone marrow culture techniques and equilibrium density centrifugation of human bone marrow cells were used to analyse the neutrophil-granulocyte, macrophage and eosinophil-granulocyte progenitor hierarchy. The buoyant density of progenitor cells changes as cells differentiate down the granulocyte-macrophage pathway an...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(82)90061-3
更新日期:1982-01-01 00:00:00
abstract::All-trans-retinoic acid (ATRA) has been proven active against a range of malignancies in isolated tissue culture systems and in human clinical trials, but the duration of its effects has been transient. Recent evidence indicates that the basis for the limited duration of ATRA's activity, at least in one form of leukem...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)90040-x
更新日期:1994-08-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell characterized by presence of the oncoprotein BCR-ABL1, which have constitutive tyrosine kinase activity. BCR-ABL1 activation induces aurora kinase A (AURKA) and aurora kinase B (AURKB) expression, which are serine-thr...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2016.06.011
更新日期:2016-09-01 00:00:00
abstract::We analyzed the biological activity of HA14-1, a small organic compound inhibitor of Bcl-2, against established leukaemia cell lines and blasts from acute myeloid leukaemia (AML) patients. HA14-1 had a potent killing activity against the leukaemia cell line that expressed endogenous or ectopic Bcl-2. This activity was...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.11.010
更新日期:2007-06-01 00:00:00
abstract::Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in acute lymphoblastic leukemia (ALL). We evaluated the C677T and A1298C polymorphisms using the TaqMan...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.10.016
更新日期:2007-09-01 00:00:00