Abstract:
:Previous studies have revealed a consistent defect in the cycling behavior of primitive neoplastic progenitor cells in patients with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML). This is manifested both in vivo and in long-term cultures of CML cells as an increased rate of turnover amongst Ph1-positive progenitor cell types whose counterparts in normal individuals are mainly quiescent. To determine whether this deregulated proliferative activity of primitive Ph1-positive cells might be explained by a perturbation in the production of growth factors that regulate the turnover of primitive normal cells, the possibility of either autocrine or paracrine mechanisms of Ph1-positive cell stimulation was investigated. Northern blot analysis of total cellular RNA extracted from various CML blood cell populations showed no evidence of increased expression of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-3, IL-6, or tumor necrosis factor-alpha (TNF-alpha) compared with analogous normal peripheral blood cell populations in which transcripts for most of these growth factors are not detectable. A similar analysis of RNA extracted from the adherent layer of 4-week-old long-term cultures established from CML marrow (in which the Ph1-positive cells typically disappear) or from CML blood seeded onto normal marrow adherent layers (in which Ph1-positive cells typically persist) also revealed no difference in growth factor production compared with analogous cultures established with exclusively normal cells. For some of the growth factors studied, the assessment of bioactivity detectable in the medium confirmed the RNA data. There was also no evidence of a decreased production of putative inhibitors of primitive hematopoietic cells, i.e. transforming growth factor-beta and macrophage inflammatory protein-1 alpha by CML versus normal cells or cultures. These results do not support the existence of BCR-ABL induced autocrine or paracrine mechanisms in CML and suggest that constitutive activation of events normally dependent on growth factor receptor stimulation is more likely to underlie the lack of proliferation control exhibited by primitive Ph1-positive cells.
journal_name
Leukemiajournal_title
Leukemiaauthors
Otsuka T,Eaves CJ,Humphries RK,Hogge DE,Eaves ACsubject
Has Abstractpub_date
1991-10-01 00:00:00pages
861-8issue
10eissn
0887-6924issn
1476-5551journal_volume
5pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::Burkitt lymphoma (BL) has a characteristic clinical presentation, morphology, immunophenotype and primary chromosomal aberration, that is, the translocation t(8;14)(q24;q32) or its variants. However, diagnostic dilemmas may arise in daily practice due to overlap of BL with subsets of other aggressive, mature B-cell ly...
journal_title:Leukemia
pub_type: 历史文章,杂志文章,评审
doi:10.1038/leu.2008.281
更新日期:2009-02-01 00:00:00
abstract::In order to further define the role of the MDR1 gene in acute myeloid leukemia (AML), we determined the association between the presence of P-glycoprotein on leukemic cells and the efficacy of therapy in patients with AML. Immunocytochemistry with monoclonal antibody C219 was performed to demonstrate the presence of P...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Between August 1978 and September 1982, 642 patients with newly diagnosed acute myelogenous leukemia (AML) were entered onto a Southwest Oncology Group Study which addressed four questions. (i) What is the comparative utility of rubidazone versus adriamycin in remission induction? (ii) What is the role of prophylactic...
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:1992-07-01 00:00:00
abstract::Allogeneic haemopoietic cell transplant (allo-HCT) may be curative in acute myeloid leukaemia (AML) in second complete remission (CR2) but the impact of reduced intensity (RIC) versus myeloablative conditioning (MAC) is uncertain. The Acute Leukaemia Working Party of the European Society for Blood and Bone Marrow Tran...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-019-0527-4
更新日期:2020-01-01 00:00:00
abstract::Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with dif...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2012.336
更新日期:2013-04-01 00:00:00
abstract::The hematopoietic growth factors are glycoproteins that can be produced by recombinant DNA technology. They have many potential clinical uses in acute leukemia; several areas have been explored extensively and much data are available from clinical trials. Other areas are of potential interest, but have a paucity of cl...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2400592
更新日期:1997-03-01 00:00:00
abstract::The interactions between haemopoietic progenitor cells and marrow stromal cells that are essential for the regulation of normal haemopoiesis are defective in chronic phase chronic myeloid leukaemia (CML). The presence of primitive progenitor cells (blast colony-forming cells, Bl-CFC) in the blood of patients with CML ...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Translocation (15;17)(q22;q12-q21) is a chromosome aberration specifically found in acute promyelocytic leukemia (APL), that generates a chimeric gene between the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARA) gene, on chromosome 17. In the course of molecular investigat...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-a subtype of Hodgkin lymphoma (HL)-is characterized by a low content of tumor cells, the lymphocyte predominant (LP) cells. Transformation into diffuse large B-cell lymphoma (DLBCL) occurs in about 10% of patients. We performed whole-genome mutation analysis of t...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2015.328
更新日期:2016-04-01 00:00:00
abstract::The antimetabolite 6-thioguanine (6-TG) is utilized in the management of acute myelogenous leukemia (AML). Angiogenesis is a possible therapeutic target in hematologic tumors. Thus, we addressed the possibility that 6-TG may also act as an anti-angiogenic molecule. 6-TG inhibited endothelial cell proliferation trigger...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402646
更新日期:2002-08-01 00:00:00
abstract::In the present study, 89 patients with generalized immunocytoma were analyzed retrospectively for the prognostic influence of clinical features and of immunophenotype using bone marrow biopsies. Univariate analysis selected the following variables as significant for survival: age over 60 years (p = 0.021), Rai and Bin...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::The requirement that leukemic Gata1 mutations be present in cells harboring trisomy 21 led to the discovery that overexpression of ERG drives aberrant megakaryopoiesis. Given that constitutive PI3K/AKT signaling is a frequent component of hematologic malignancies and the relationship between AKT and Notch in this line...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.33
更新日期:2013-06-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytok...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402703
更新日期:2002-11-01 00:00:00
abstract::In this report, a Radiation leukemia virus-transformed murine T cell lymphoma is described which is dependent on the interleukin-2 (IL-2) growth factor for proliferation under single cell conditions of growth. It was isolated from a C57BL mouse which had been primed with the Radiation leukemia virus-induced thymoma, C...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::We have investigated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and several potent vitamin D3 analogs [1,25(OH)2-16-ene-23-yne-D3; 1,25(OH)2-16-ene-23-yne-26,27-F6-D3] on productive infection by human immunodeficiency virus (HIV) in human macrophages. Macrophages derived from the peripheral blood were eithe...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::Epigenetic deregulation is involved in acute myeloid leukemia (AML) pathogenesis and epigenetic targeting drugs are in clinical trial. Since the first results with histone-deacetylase inhibitors in AML are controversial, novel single and combined treatments need to be explored. It is tempting to combine chromatin-targ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.271
更新日期:2012-04-01 00:00:00
abstract::Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). The Fv-4' env antigen that binds to the cell surface of Fv-4'-bearing C3H cells was found in sera from normal Fv-4'-bearing C4W mice. The serum Fv-4' env antigen binds to ecotropic MuLV receptors, shown by s...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::In order to assess the proliferative capacity of leukemic subpopulations and to know whether it can be related to the stage of maturation, the expression of two surface antigens identifying distinct steps of leukocyte differentiation (CD15 and CD34) was studied by flow cytometry in correlation with DNA content in 16 c...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::We applied a new strategy for the detection of N-ras gene mutations based on LightCycler technology. We designed two sets of amplimers and internal hybridization probes representing N-ras codons 12/13 and codon 61, respectively. Genomic DNAs from 134 childhood acute lymphoblastic leukemia (ALL) patients (83 common ALL...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401645
更新日期:2000-02-01 00:00:00
abstract::The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed "minimal residual disease". The phenomenon of disease persistence suggests that despite tar...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-019-0684-5
更新日期:2020-06-01 00:00:00
abstract::Drug resistance is a growing area of concern. It has been shown that a small, residual pool of leukemic CD34+ progenitor cells can survive in the marrow microenvironment of chronic myeloid leukemia (CML) patients after years of kinase inhibitor treatment. Bone marrow (BM) stroma has been implicated in the long-term su...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.360
更新日期:2012-05-01 00:00:00
abstract::We report here the case of a 55-year-old patient with chronic granular lymphocyte disorder associated with moderate neutropenia. The majority of peripheral blood lymphocytes displayed a CD3-, CD8-, CD16+, CD56(NKH1)- phenotype. The patient's cells showed high spontaneous cytotoxic activity against K562 targets and dev...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::With a seroprevalence rate (SPR) of 6%-10% among healthy adult blood donors (ABD), Nigeria and other African locales represent an endemic zone for HTLV-I. We studied SPR in patients with leukaemia, lymphomas, solid tumours, and chronic disorders, as well as in groups of men and women with varying sexual lifestyles. Se...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Patients with chronic lymphocytic leukemia (CLL) have defects in both cellular and humoral immunity. Since CD152 (CTLA-4) plays a critical role in downregulating T-cell responses, we studied the expression of surface and cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells from treatment-naï...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403907
更新日期:2005-10-01 00:00:00
abstract::The adult marrow hematopoietic stem cell biology has largely been based on studies of highly purified stem cells. This is unfortunate because during the stem cell purification the great bulk of stem cells are discarded. These cells are actively proliferating. The final purified stem cell is dormant and not representat...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2017.155
更新日期:2017-08-01 00:00:00
abstract::Current MRD studies in T-cell acute lymphoblastic leukemia (T-ALL) mainly use T-cell receptor gamma, delta and SIL-TAL1 gene rearrangements as MRD-PCR targets. However, low frequency or limited diversity of these markers restricts the number of evaluable patients, particularly because two markers are recommended for M...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403263
更新日期:2004-04-01 00:00:00
abstract::The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only been reported on cells of myeloid and monocytic origin. In the present study,...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::During infection with different retroviruses, high levels of unintegrated extrachromosomal DNA accumulate in infected cells. While extrachromosomal linear DNA is the immediate precursor of the integrated provirus, the function, if any, of extrachromosomal circular DNA has been unclear. Several groups have attempted to...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2400776
更新日期:1997-09-01 00:00:00
abstract::The discovery of almost identical or 'stereotyped' B-cell receptor immunoglobulins (BcR IG) among unrelated patients with chronic lymphocytic leukemia (CLL) cemented the idea of antigen selection in disease ontogeny and evolution. The systematic analysis of the stereotypy phenomenon in CLL revealed that around one-thi...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2016.322
更新日期:2017-02-01 00:00:00
abstract::Deletions from the derivative chromosome 9, der(9), of the translocation, t(9;22)(q34;q11), at the site of the ABL/BCR fusion gene, have been demonstrated by fluorescence in situ hybridisation (FISH), in both Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL)....
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403629
更新日期:2005-04-01 00:00:00