Abstract:
:Despite recent advances in our understanding of the molecular and biological abnormalities in chronic myelogenous leukemia (CML) this new knowledge has not yet led to significant improvements in treatment. We have reviewed what is known and still unknown about the molecular and biological abnormalities in CML that may be relevant to developing improved, more selective treatment. CML originates in a multipotential stem cell due to its acquiring a highly consistent specific chromosomal translocation between chromosomes 9 and 22; this results in a fused bcr/abl gene and an abnormal 210 kDa fusion protein which has increased intrinsic protein tyrosine kinase activity compared to the normal c-abl protein. It is still unknown how p210bcr-abl alters the signal transduction pathways, but the main biological abnormality is discordant or asynchronous maturation, with the cytoplasm generally maturing more rapidly than the nucleus. The major expansion of the CML population takes place in the intermediate and later maturation compartments rather than in the stem cell or early progenitor cell compartments. The expansion occurs slowly, probably taking several years to reach a trillion or more cells, at which time clinical symptoms begin to develop. The maturing leukemic progenitors do not have an increased proliferative rate, but they undergo one or more additional divisions and also live longer than comparable normal progenitors. The earliest CML blast cell population we have been able to study has reduced ultimate proliferative capacity compared to a comparable primitive normal blast cell population. Although no quantitative stem cell assay is available, indirect evidence suggests that the CML stem cells' biological behavior may be relatively unaffected or deviate only slightly from normal. The bcr/abl gene and its fusion protein are promising targets for development of novel specific therapies, but before this can be accomplished it will be necessary to understand more completely the molecular and biochemical abnormalities and to correlate them with the biological manifestations of the disease.
journal_name
Leukemiajournal_title
Leukemiaauthors
Clarkson B,Strife Asubject
Has Abstractpub_date
1993-11-01 00:00:00pages
1683-721issue
11eissn
0887-6924issn
1476-5551journal_volume
7pub_type
杂志文章,评审相关文献
LEUKEMIA文献大全abstract::Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Bovine leukemia virus-infected sheep were demonstrated to possess a plasma factor that specifically suppresses in vitro virus expression in lymphocyte cultures. This blocking activity is observed even after phytohemagglutinin (PHA) stimulation and is independent of cellular proliferation. Such a factor may play a crit...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-02-01 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::CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosi...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2017.301
更新日期:2018-01-01 00:00:00
abstract::Immunofluorescent staining of peripheral blood mononuclear cells with the monoclonal antibody anti-HC2 combined with phase microscopic examination identified leukemic hairy cells in nine of 13 patients (69%) evaluated at Memorial Hospital prior to treatment with recombinant alpha-interferon (rIFN-alpha A). The remaini...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day, days 1-3; cytarabine 150 mg/m2/day, days 1-7; aclarubicin 12 mg/m2/day, days 1-7) as an induction therapy in the treatment of de novo acute myeloid leukemia (AML), 48 patients with newly diagnosed AML, aged 35 (14-57) years, were entered ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404287
更新日期:2006-08-01 00:00:00
abstract::The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyur...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Identification of rearrangements in the immunoglobulin heavy chain (IgH), T cell receptor (TCR) and other genes assists in the classification of hemopoietic disorders. This study reviews a 5 year experience of genotyping as an assessment of clonality in a central referral laboratory. Patients were referred for assessm...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2400678
更新日期:1997-06-01 00:00:00
abstract::Cytogenetic evolution in the myelodysplastic syndrome (MDS) has been associated with an abrupt shift to acute myelogenous leukemia (AML). To investigate the 'evolution' of MDS to AML we compared the karyotypes of MDS patients at presentation and at development of AML. Of 170 patients with MDS who developed AML, 63 had...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2014.60
更新日期:2014-08-01 00:00:00
abstract::Normal human myeloid cells require certain colony stimulating factors (CSFs) for growth and differentiation. These CSFs are normally produced exogenously by accessory cells. However, human acute myeloid leukemia cells have been found, in certain instances, to have constitutive, endogenous production of one or more of ...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Many agents have been known to induce the differentiation of HL-60 cells. However, only a small number of reports on the basophilic differentiation of this cell line are known. In this study we show that the exposure of HL-60 cells to chloroquine induces to differentiate into basophils. This chloroquine-induced change...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::We studied 174 consecutive patients with relapsed refractory multiple myeloma (MM) enrolled on a phase II clinical trial of pomalidomide plus low-dose dexamethasone at Mayo Clinic. Extramedullary disease (EMD) was present at the time of trial entry in 7.5% (13 of 174 patients). The rate of EMD in the first 3 years fol...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.29
更新日期:2011-06-01 00:00:00
abstract::Transplantation of normal and malignant human hematopoietic cells into severe combined immunodeficient (SCID) mice allows for evaluation of long-term growth abilities of these cells and provides a preclinical model for therapeutic interventions. However, large numbers of cells are required for successful engraftment i...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2400694
更新日期:1997-07-01 00:00:00
abstract::Here we describe the results of an interlaboratory test for RT-PCR-based BCR/ABL analysis. The test was organized in two parts. The number of participating laboratories in the first and second part was 27 and 20, respectively. In the first part samples containing various concentrations of plasmids with the ela2, b2a2 ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401899
更新日期:2000-10-01 00:00:00
abstract::These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [tabl...
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:1992-01-01 00:00:00
abstract::Human T-lymphotropic virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia/lymphoma (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In both diseases, expression of viral message can generally only be demonstrated by the reverse transcriptase-polymerase chain reaction...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::The chimeric fusion oncogene early B-cell factor 1-platelet-derived growth factor receptor-β (EBF1-PDGFRB) is a recurrent lesion observed in Philadelphia-like B-acute lymphoblastic leukemia (B-ALL) and is associated with particularly poor prognosis. While it is understood that this fusion activates tyrosine kinase sig...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.166
更新日期:2018-01-01 00:00:00
abstract::We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.101
更新日期:2016-10-01 00:00:00
abstract::PCR-based monitoring of minimal residual disease (MRD) in acute leukemias can be achieved via detection of fusion gene transcripts of chromosome aberrations or detection of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements. We wished to assess whether both PCR targets are complementary in acute myeloid...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402387
更新日期:2002-03-01 00:00:00
abstract::Analysis at the DNA and RNA level revealed a mature genetic marker profile in a case of T type blast crisis of chronic myelocytic leukemia. T cell receptor beta chain gene rearrangement as well as T cell receptor alpha mRNA transcription was demonstrated in blasts of the malignant clone. Corresponding findings were ob...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Adolescents had lower rates of remission induction and shorter event-free survival than younger children in this study of consecutively treated patients with acute lymphoblastic leukemia (ALL). When compared to the younger patients (ages 1-9 years; n = 995), adolescents (ages 10-21 years; n = 338) were significantly m...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1990-02-01 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::The t(14;18) chromosomal translocation occurs in most follicular non-Hodgkin's lymphomas and places the Bcl-2 gene on chromosome 18q21 into the immunoglobulin JH region on chromosome 14q32. This translocation can be exploited to detect clonal malignant cells bearing this genetic alteration. A polymerase chain reaction...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::We have previously reported that constitutive expression of c-fos oncogene allows long-term proliferation of primary mouse bone marrow stromal cells favoring the granulocytic differentiation of myeloid precursors in an in vitro assay. Retrovirus-mediated gene transfer of the human c-fos gene was used here for immortal...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by clonal proliferation of plasma cells and a heterogenous genomic landscape. Copy number and structural changes due to chromosomal instability (CIN) are common features of MM. In this review, we describe how primary and secondary genetic event...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/s41375-020-0921-y
更新日期:2020-11-01 00:00:00
abstract::We analyzed the long-term outcome of 1011 patients treated in five successive clinical trials (Total Therapy Studies 11, 12, 13A, 13B, and 14) between 1984 and 1999. The event-free survival improved significantly (P=0.003) from the first two trials conducted in the 1980s to the three more recent trials conducted in th...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/leu.2009.252
更新日期:2010-02-01 00:00:00
abstract::We have previously shown that chronic lymphocytic leukemia (CLL) B cells secrete vascular endothelial growth factor (VEGF) in vitro, have constitutively active VEGF receptors R1 and R2, and respond to exogenous VEGF by specifically upregulating Mcl-1 and XIAP in association with decreased cell death. We found that epi...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403667
更新日期:2005-04-01 00:00:00
abstract::Resistant AML encompasses two groups of patients: those with refractory leukemia and those whose leukemia has relapsed. Refractory leukemia is disease that does not respond to initial induction chemotherapy with cytarabine and an anthracycline. Patients with refractory leukemia are likely to have disease with adverse ...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1998-09-01 00:00:00
abstract::Novel approaches have been designed to treat leukemia based on our understanding of the genetic and biochemical lesions present in different malignancies. This meeting report summarizes some of the recent advances in leukemia treatment. Based on the discoveries of cellular oncogenes, chromosomal translocations, monocl...
journal_title:Leukemia
pub_type:
doi:10.1038/sj.leu.2403156
更新日期:2003-12-01 00:00:00