Abstract:
:As a result of the introduction of new sequencing technologies, the molecular landscape of acute myeloid leukemia (AML) is rapidly evolving. From karyotyping, which detects only large genomic aberrations of metaphase chromosomes, we have moved into an era when sequencing of each base pair allows us to define the AML genome at highest resolution. This has revealed a new complex landscape of genetic aberrations where addition of mutations in epigenetic regulators has been one of the most important contributions to the understanding of the pathogenesis of AML. These findings, together with new insights into epigenetic mechanisms, have placed dysregulated epigenetic mechanisms at the forefront of AML development. Not only have several new mutations in genes directly involved in epigenetic regulatory mechanisms been discovered, but also previously well-known gene fusions have been found to exert aberrant effects through epigenetic mechanisms. In addition, mutations in epigenetic regulators such as DNMT3A, TET2, and ASXL1 have recently been found to be the earliest known events during AML evolution and to be present as preleukemic lesions before the onset of AML. In this article, we review epigenetic changes in AML also in relation to what is known about their mechanism of action and their prognostic role.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Eriksson A,Lennartsson A,Lehmann Sdoi
10.1016/j.exphem.2015.05.009subject
Has Abstractpub_date
2015-08-01 00:00:00pages
609-24issue
8eissn
0301-472Xissn
1873-2399pii
S0301-472X(15)00191-5journal_volume
43pub_type
杂志文章,评审abstract::In vitro studies of human hemopoiesis are often limited by the availability of normal bone marrow. We have overcome this difficulty by taking advantage of the bone marrow fragments removed during total hip replacement. We report here a comparative study of the colony forming capacity of trochanter and sternal or iliac...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::Mouse hematopoietic stem cells (HSCs) are highly enriched in the rare (approximately 0.05%) Thy-1.1(lo)Lin(-/lo)Sca-1+ fraction of hematopoietic tissues. It has been demonstrated that Thy-1.1(lo)Lin(-/lo)Sca-1+ cells are the only HSCs in C57BL/Ka-Thy-1.1 bone marrow. In this study, we separated C57/Ka-Thy-1.1 bone mar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PE...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Differentiation- and lineage-related differences in the expression of two anti-apoptotic molecules, bcl-x and bcl-2, were examined using various human hematopoietic cell lines. Bcl-x was strongly expressed in cell lines with erythroid and megakaryocytic properties (K562, HEL, CMK, and Mo7E), and was moderately express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results r...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.08.028
更新日期:2008-01-01 00:00:00
abstract::Nasal natural killer-T cell lymphoma (NNKTL) is associated with the Epstein-Barr virus and has distinct histologic features, such as angiocentric and polymorphous lymphoreticular infiltrates that contain too many cell types, including tumor and inflammatory cells. We have shown previously that intercellular adhesion m...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.03.009
更新日期:2013-08-01 00:00:00
abstract::Antisera from rabbits immunized with murine macrophage colony-stimulating factor (CSF-1) were evaluated for cross-reactivity with human urine CSF-1. One cross-reactive antiserum was used to purify CSF from human urine. The IgG fractions from normal rabbit serum and the anti-CSF serum were bound to cyanogen bromide-act...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:Regulation of the cell cycle by cyclin-dependent kinase (CDK) activity occurs at multiple levels and is often altered in human cancers. Therefore, CDK activity has been targeted for drug discovery, and a number of small molecules have now been identified as CDK inhibitors. Plant cytokinin analogues with CDK i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00894-9
更新日期:2002-10-01 00:00:00
abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract:OBJECTIVE:Hematopoietic stem cells (enriched in fraction of CD34+ cells) have the ability to regenerate hematopoiesis in all of its lineages, and this potential is clinically used in transplanting bone marrow or peripheral blood stem cells. Our objective was to assemble a suitable method for evaluating gene expression ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.006
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVES:Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Fur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2008.07.009
更新日期:2008-11-01 00:00:00
abstract::The bcr/abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia (CML). The Haseloff and Gerlach model was used to design a ribozyme targeted to this transcript. When tested against a synthetic substrate covering the translocation sequence, the ribozyme exhibited si...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::The circadian and circannual rhythms of committed stem cells (CFUc) were investigated by using the agar colony technique. There was a marked circadian rhythmicity, with variations between maximum and minimum colony yields of 2-5.5 times; such variations could also be seen throughout the year. A phase shift was observe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Fabry disease is a lysosomal storage disorder that is due to a deficiency in alpha-galactosidase A (alpha-gal A). Previously we have shown that a recombinant retrovirus synthesized for the transfer of the human alpha-gal A coding sequence was able to engineer enzymatic correction of the hydrolase deficiency in fibrobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00050-8
更新日期:1999-07-01 00:00:00
abstract::Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion mo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00031-9
更新日期:1999-02-01 00:00:00
abstract::Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutrali...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract:OBJECTIVE:These studies were performed to test the hypothesis that DNMT1 is required for maintenance of DNA methylation and repression of the γ-globin gene in adult-stage erythroid cells. MATERIALS AND METHODS:DNMT1 levels were reduced by nucleofection of small interfering RNA targeting DNMT1 in chemical inducer of di...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.10.003
更新日期:2011-01-01 00:00:00
abstract::The effects of chronic exposure to graded hypoxia (inspired PO2 = 146, 90, 78, 73 and 60 torr) on the development of hypoxia-induced hemoglobinemia and the rate of hemoglobin degradation in intact and acutely splenectomized rats were studied. Hemoglobin mass increased with hypoxia over the whole range studied. Hemoglo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::The production of interferon-alpha (IFN-alpha) by normal human peripheral blood mononuclear cells (PBMNC) was studied using polyclonal antipeptide antibodies designed to react either with all IFN-alpha subtypes or with individual subtypes IFN-alpha 2 or IFN-alpha 4. In this study, we demonstrate the detection of intra...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::The prototypic human acute phase reactant, C-reactive protein (CRP), and a structurally modified form of CRP (mCRP) were studied as agents which could stimulate thrombopoiesis in both in vitro and in vivo mouse models. mCRP, but not the widely studied (native) pentameric form of CRP, demonstrated significant megakaryo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Interferon (INF)-α was the maintenance treatment of choice after autologous stem cell transplantation in multiple myeloma in the past, but currently Thalidomide is commonly used. In this prospective study, the implications of the various types of maintenance therapy on the patients T cell pattern and activation status...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2012.10.018
更新日期:2013-03-01 00:00:00
abstract::The presence of granulocyte colony-stimulating factor receptor (G-CSFR) in CD34+ hematopoietic progenitors is demonstrated by flow cytometry. Cord blood mononuclear cells (MNCs) contain about 1.09 +/- 0.2% CD34+ cells, 0.32 +/- 0.1% CD34+/G-CSFR+ (G-CSFR+) cells, and 0.77 +/- 0.1% CD34+/G-CSFR- (G-CSFR-) cells. The co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::The mechanism of accelerated erythropoiesis under the hypoxic conditions of high altitude (HA) remains largely obscure. Here, we investigated the potential role of bone marrow (BM) T cells in the increased production of erythrocytes at HA. We found that mice exposed to a simulated altitude of 6,000 m for 1-3 weeks exh...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.04.007
更新日期:2014-09-01 00:00:00
abstract::Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal because of a defect in definitive hematopoiesis; however, the significance of AM in embryonic hematopoiesis remains unknown. This study characterized the hematop...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.01.002
更新日期:2014-05-01 00:00:00
abstract::To clarify the effects of androgen on hemopoiesis in mice, we investigated changes in hemopoietic stem cells at various stages of differentiation after injection of 19-nandrolone decanoate (19-ND). 19-ND induced (a) a marked increase in the population of CFUe, especially in the spleen, and (b) a less significant incre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::Drug resistance remains a serious problem in leukemia therapy. Among newly developed nucleoside antimetabolites, clofarabine has broad cytotoxic activity showing therapeutic promise and is currently approved for relapsed acute lymphoblastic leukemia. To investigate the mechanisms responsible for clofarabine resistance...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.11.001
更新日期:2015-03-01 00:00:00
abstract::Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow tar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00