Abstract:
:A poorly defined transforming event(s) affects the pluripotential bone marrow (BM) stem cell in myelodysplastic syndromes (MDS), conferring a growth advantage upon it which leads eventually to monoclonal hematopoiesis. The progeny of this transformed ancestor undergo recognizable albeit dysplastic maturation. We propose that this picture is further complicated by a variety of cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and interleukin 1beta (IL-1beta) which exert a dual effect on the diseased cells. The immature CD34+ cells are stimulated to proliferate, while their later differentiated daughters are induced to undergo apoptosis accounting for the clinical syndrome of pancytopenia despite hypercellular BMs. Studies directed at measuring the rates of proliferation and apoptosis as well as the levels of TNF-alpha, TGF-beta and IL-1beta confirm this hypothesis and are presented in greater detail. A novel approach towards MDS therapy emerges as a result of this paradigm shift based upon the premise that anti-cytokine therapy would prevent excessive intramedullary apoptosis and result in improved cytopenias as well as cause a slowing down of the diseased precursor cell proliferation resulting in resumption of polyclonal hematopoiesis. Because a number of cytokines function through common lipid second messengers, interruption of this pathway should theoretically cause disruption in the signalling of a cascade of cytokines.
journal_name
Leukemiajournal_title
Leukemiaauthors
Raza A,Mundle S,Shetty V,Alvi S,Chopra H,Span L,Parcharidou A,Dar S,Venugopal P,Borok R,Gezer S,Showel J,Loew J,Robin E,Rifkin S,Alston D,Hernandez B,Shah R,Kaizer H,Gregory S,Preisler Hsubject
Has Abstractpub_date
1996-10-01 00:00:00pages
1648-52issue
10eissn
0887-6924issn
1476-5551journal_volume
10pub_type
杂志文章,评审相关文献
LEUKEMIA文献大全abstract::Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease that currently lacks genomic and genetic biomarkers to assist in its clinical management. We performed whole-exome sequencing (WES) of three BPDCN cases. Based on these data, we designed a resequencing approach to identify mutations in 38 sele...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.283
更新日期:2014-04-01 00:00:00
abstract::All-trans-retinoic acid (ATRA) is highly active in acute promyelocytic leukemia but not in other types of acute myeloid leukemia (AML). Previously, we showed that ATRA in combination with Lysine-specific demethylase 1 (LSD1) inhibition by tranylcypromine (TCP) can induce myeloid differentiation in AML blasts. This pha...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-020-0892-z
更新日期:2020-06-19 00:00:00
abstract::The purpose of this study was to determine the incidence of and pharmacokinetic parameters associated with the development of transient encephalopathy following the administration of high-dose methotrexate and intrathecal chemotherapy in children with acute lymphoblastic leukemia (ALL). Two hundred and fifty-nine chil...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/sj.leu.2401098
更新日期:1998-08-01 00:00:00
abstract::The 2001 World Health Organization (WHO) treatise on the classification of hematopoietic tumors lists chronic myeloproliferative diseases (CMPDs) as a subdivision of myeloid neoplasms that includes the four classic myeloproliferative disorders (MPDs)-chronic myelogenous leukemia, polycythemia vera (PV), essential thro...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2404955
更新日期:2008-01-01 00:00:00
abstract::Tumorigenesis can be considered as pathologically misappropriated tissue regeneration. In this review we will address some unresolved issues that support this concept. First, we will address the issue of the identity of cancer-initiating cells and the presence of cancer stem cells in growing tumors. We will also ask a...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/s41375-018-0294-7
更新日期:2018-12-01 00:00:00
abstract::A lot of genes deregulated in malignant plasma cells (PCs) involved in multiple myeloma have been reported these last years. The expression of some of these genes is associated with poor survival. A critical step is to elucidate the biological mechanisms triggered by these gene products. Such studies are hampered by t...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2012.36
更新日期:2012-07-01 00:00:00
abstract::Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childh...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402815
更新日期:2003-02-01 00:00:00
abstract::We present the long-term results of three consecutive clinical trials (Total Therapy studies 11, 12 and 13A) conducted for children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1984 and 1994. In study 11 (1984-1988), the overall event-free survival rates (+/-1 s.e.) were 71.8 +/- 2.4% and 69.3 +/- 2...
journal_title:Leukemia
pub_type: 杂志文章,meta分析
doi:10.1038/sj.leu.2401938
更新日期:2000-12-01 00:00:00
abstract::Monoclonal antibody (mAb) M195 is a mouse IgG2a reactive with a myelomonocytic differentiation antigen found on early myeloid cells and monocytes. The reactivity of M195 with fresh hematopoietic neoplasms in the blood or bone marrow from 227 patients at Memorial Hospital was determined by flow cytometry. M195 was posi...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia (GVL) effects determining transplant outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cell...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404892
更新日期:2007-10-01 00:00:00
abstract::Disturbances in the regulation of the balance between the fibrinolytic and procoagulant properties of leukemic cells may contribute to the coagulopathy of acute leukemia. The coagulant response to a number of stimuli is regulated by the expression of tissue factor, but the role of the plasminogen activator inhibitors,...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::We have analysed the structure of the T-cell receptor gamma chain (TCRG) genes in a panel of biopsies taken from 24 patients with acute lymphoblastic leukemia (ALL) (13 cALL, one pre-B ALL, two null ALL and eight T-ALL) at presentation and at clinical relapse. In the majority of cases (18/24) the structure of these ge...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::We analyzed mRNA expression of the flt3 gene in 30 patients with acute myeloid leukemia (AML) and 50 with acute lymphoblastic leukemia (ALL). Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of flt3 was observed in 61 patients; 22 (73%) with AML and 39 (78%) with ALL. Among these, five patien...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::Large granular lymphocyte leukemia (LGLL) is a rare and chronic lymphoproliferative disorder characterized by the clonal expansion of LGLs. LGLL patients can be asymptomatic or develop cytopenia, mostly neutropenia. Somatic STAT3 and STAT5b mutations have been recently reported in approximately 40% of patients. The ai...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/s41375-019-0644-0
更新日期:2020-04-01 00:00:00
abstract::Histone acetyltransferases (HATs) catalyze the transfer of an acetyl group from acetyl-CoA to lysine residues of histones and play a central role in transcriptional regulation in diverse biological processes. Dysregulation of HAT activity can lead to human diseases including developmental disorders and cancer. Through...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-020-1001-z
更新日期:2020-08-06 00:00:00
abstract::The effect of deoxycytidine (dCyd) on the inhibitory effects of two antileukemic nucleoside analogs, 5-aza-2'-deoxycytidine and ara-5-aza-Cyd, toward the clonogenic growth of normal human bone marrow progenitors (CFU-GM) and leukemic blast progenitors (L-CFU) was examined. Continuous exposure of cells to 10(-6)-10(-5)...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-018-0144-7
更新日期:2018-11-01 00:00:00
abstract::Many chemotherapeutic agents induce apoptosis in tumor cells, but killing of normal cells remains a major obstacle. Development of multidrug resistance further limits chemotherapy in cancer. Here, I show that multidrug resistance can be exploited for selective killing of multidrug-resistant cells by a combination of a...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402127
更新日期:2001-06-01 00:00:00
abstract::Ligation of CD40 on chronic lymphocytic leukemia (CLL) cells induces phenotypic and biochemical changes that facilitate CLL cell-T cell interactions and enhances the sensitivity of CLL cells to clearance by adaptive and innate immune-effector mechanisms. CLL cells can be transduced to express CD40 ligand (CD154) using...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2010.191
更新日期:2010-11-01 00:00:00
abstract::Heterozygous and homozygous deletions of chromosome 13q14.3 are found in 50% of patients with B cell CLL, suggesting the presence of one or more tumour suppressor genes within the deleted region. To identify candidate genes from the region, we constructed a map of 13q14.3 using a combination of genomic and cDNA librar...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402551
更新日期:2002-07-01 00:00:00
abstract::Acute leukemias of the t(4;11) (MLL-AF4 fusion gene) type frequently have high white blood counts and extramedullary disease in multiple organs. In the present study we evaluated the hypotheses that this extensive disease is the result of extramedullary survival of leukemia cells due to resistance to stress-induced ce...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401148
更新日期:1998-10-01 00:00:00
abstract::Employing a multicolour flow cytometry assay, 133 B-chronic lymphocytic leukaemia (B-CLL) cases were analysed for surface expression of CD38. Based on a cut-off value of 20%, CLL patients were categorised into a CD38-positive (> or = 20%, n = 56) and a CD38-negative subgroup (< 20%, n = 77) and separately analysed for...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402339
更新日期:2002-01-01 00:00:00
abstract::During the 15 year period 1975-1989, 74 cases of chronic myeloproliferative disorder (CMPD) were cytogenetically analyzed in our department. Thirty patients had polycythemia vera (PV), 23 had idiopathic myelofibrosis (MFS), 15 had idiopathic thrombocythemia (IT), and six had unclassifiable CMPD (UCMPD). The overall fr...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1991-03-01 00:00:00
abstract::The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) in patients with advanced low-grade non-Hodgkin's lymphomas in way of a prospective randomized multicenter trial. Two hundred and forty-six patie...
journal_title:Leukemia
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1996-05-01 00:00:00
abstract::The combination of the anti-viral agents, zidovudine (AZT) and interferon-alpha (IFN), is a potent treatment of HTLV-I-associated adult T cell leukemia/lymphoma (ATL). In this study we investigate the possible mechanism of action of this combination by examining several cellular parameters including cell proliferation...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401742
更新日期:2000-04-01 00:00:00
abstract::The monitoring of chimerism by PCR has become a routine diagnostic approach in patients after allogeneic bone marrow or peripheral blood stem cell transplantation. Nevertheless, a temporal correlation between molecular and hematologic assessment of engraftment has not been clearly established. To address this issue, a...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT an...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2015.98
更新日期:2015-09-01 00:00:00
abstract::Two hundred and forty-four untreated acute myelogenous leukemia (AML) patients with unfavorable karyotypes and 109 others with favorable aneuploid karyotypes were used to evaluate the prognostic significance of having both normal and abnormal metaphases (AN) vs only abnormal metaphases (AA) at AML presentation. The AA...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract::To guide development of new clinical strategies, a review of recent investigations in the pathobiology of MDS was performed. Articles were identified through a Medline search. Studies, including reviews, are cited in the references. A multistep pathogenesis is proposed. (1) Targeted injury or mutation within hemopoiet...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2401618
更新日期:2000-01-01 00:00:00
abstract::Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I ...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2014.127
更新日期:2014-10-01 00:00:00