Abstract:
:The chemicals 6-mercaptopurine (6-MP) and methotrexate (MTX) are the cornerstones in the maintenance treatment of acute lymphoblastic leukemia. The intracellular metabolism of 6-MP to 6-thioguanosine nucleotides (TGN) via 6-thioinosine 5'-monophosphate (TIMP) is crucial for its cytotoxic effect. MTX inhibits purine de novo synthesis and thereby increases the intracellular PRPP being a substrate for the phosphoribosylation of 6-MP to TIMP. Hypoxanthine has been shown to inhibit the uptake of 6-MP over the cell membrane and the phosphoribosylation of 6-MP to TIMP. We have previously shown that the conversion of TIMP to TGN decreases at 6-MP concentrations above 5 microM in vitro. The aim of the present study was therefore to investigate the effect of MTX increasing the PRPP and TIMP concentrations and of hypoxanthine decreasing the TIMP concentration on the formation of TGN from TIMP. Murine myelomonocytic leukemia cells (WEHI-3b) were treated with 6-MP in vitro. The drug concentration was kept constant by continuous addition of 6-MP during the experiment. With this technique, the concentration of TGN begins to decrease already at 6-MP concentrations above 2 microM. The addition of 0.2 microM MTX 6 h before 6-MP strongly inhibited the purine de novo synthesis, decreased the ATP, and increased the PRPP concentration 4-fold. The intracellular concentrations of TIMP and to a lesser extent TXMP also increased. The concentrations of the TGN were, however, basically unaffected by the preincubation with MTX. Simultaneous addition of 20-50 microM hypoxanthine and 6-MP decreased the accumulation of all cellular 6-MP metabolites. It is concluded that the synergistic cytotoxic effect of the combination of 6-MP and MTX is not based on biochemical modulation of the 6-MP metabolism by MTX.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Liliemark J,Pettersson B,Peterson Cdoi
10.1016/0145-2126(92)90065-fkeywords:
subject
Has Abstractpub_date
1992-01-01 00:00:00pages
275-80issue
3eissn
0145-2126issn
1873-5835journal_volume
16pub_type
杂志文章abstract::Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in normal human and in malignant lymphoid cells. Thymocytes had high ADA activity (21.2 +/- 6.8 10(3) nM/h/mg) and low PNP activity (1.2 +/- 0.6), whereas T peripheral blood lymphocytes (PBL) had low ADA activity (1.20 +/- 0.22) and high...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(82)90027-3
更新日期:1982-01-01 00:00:00
abstract::FLT3 is a receptor tyrosine kinase involved in the survival of hematopoietic stem cells, and mutations of FLT3 have been reported to be of prognostic significance. This is the first study of FLT3 mutations in pediatric non-promyelocytic AML patients that received the same treatment scheme in single institute. FLT3 int...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.11.006
更新日期:2005-06-01 00:00:00
abstract::Several genetic polymorphisms in the genes coding folate-metabolizing enzymes have been associated with susceptibility to hematology malignancies. We conducted a Korean population-based case-control study to examine the relationship between the polymorphisms of folate-metabolizing enzymes and the risk of AML (acute my...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.07.026
更新日期:2009-01-01 00:00:00
abstract::miR-16, a miRNA involved in cell proliferation and apoptosis regulation, may interfere with either oncogenic or tumor-suppressor pathways and is implicated in leukemogenesis. We then explored its expression in 93 childhood acute lymphoblastic leukemia (ALL) cases. A high miR-16 expression was associated with hyperleuk...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.12.015
更新日期:2009-09-01 00:00:00
abstract::Chronic myelogenous leukemia (CML) and 25% of adult onset acute lymphoblastic leukemia (ALL) are associated with the expression of Bcr-Abl, a constitutively activated protein tyrosine kinase. Bcr-Abl associated leukemias are characterized by a high degree of chromosomal and genomic instability. It is unclear if the ph...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(01)00181-3
更新日期:2002-11-01 00:00:00
abstract::Leukotrienes and lipoxins are bioactive lipoxygenase products formed by leukocytes alone or in collaboration with other cells. While the physiological role of lipoxins remains to be clarified, accumulating evidence shows that leukotrienes are important mediators in asthma and inflammation. Consequently, recent clinica...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/0145-2126(94)90053-1
更新日期:1994-10-01 00:00:00
abstract::In a patient affected with chronic lymphocytic leukemia with lymphocyte surface mu and kappa determinants and vacuolated bone marrow plasma cells, the serum contained polymers of a truncated mu chain and normal-sized kappa chains. These light chains were present as monomers and covalent dimers in studies performed und...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90129-9
更新日期:1993-06-01 00:00:00
abstract::Introduction of the maturation index (MI) as a measure for the degree of maturation improved the subtyping of acute myeloid leukemia (AML). A comparison is made here between the MI and the results of surface marker analysis with a panel of monoclonal antibodies (McAb) in the immunofluorescence technique. The McAb appl...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(83)90100-5
更新日期:1983-01-01 00:00:00
abstract::The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibit...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(85)90006-2
更新日期:1985-01-01 00:00:00
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journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(95)00084-4
更新日期:1995-12-01 00:00:00
abstract::Like CD19 or CD56, CD22 in non-lymphoid leukemia has been considered an aberrantly expressed antigen. CD22 had been believed to be restricted to B lymphoid, however, it was also found to be expressed in human basophils. Mature basophils are unique granulocytes expressing CD13, CD22 and CD25. To estimate whether the ex...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2003.10.034
更新日期:2004-07-01 00:00:00
abstract::The CBFA2 gene on chromosome band 21q22 is one of the most commonly translocated genes in leukemia. As with other translocations, those involving CBFA2 are associated with specific disease phenotypes. Only one of the different translocations involving CBFA2, the t(12;21), has been associated with a non-myeloid lineage...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(99)00150-2
更新日期:2000-01-01 00:00:00
abstract::We hypothesized that the high early death rate (EDR) due to bleeding in acute promyelocytic leukemia (APL) is in part attributable to delays in all- trans retinoic acid (ATRA). We conducted a retrospective analysis of the timing of ATRA administration. 204 consecutive patients with newly diagnosed APL between 1992 and...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2013.05.007
更新日期:2013-09-01 00:00:00
abstract::To evaluate the clinical usefulness of interleukin 2 (IL-2) on myelodysplastic syndromes (MDS), the serum IL-2 level, the effect of IL-2 on the proliferation of blasts, and the cell-mediated cytotoxic effect of IL-2 on blasts were examined in MDS patients. Of 18 patients, 2 patients had an increased serum IL-2 level. ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90058-s
更新日期:1993-02-01 00:00:00
abstract::The aim of this study was to evaluate effect of c-KIT mutations on RUNX1/RUNX1T1 fusion transcript expression in patients with t(8;21)-positive AML. Fifty patients diagnosed with t(8;21)-positive AML for recent 10 years were enrolled. Patients with c-KIT mutations tended to achieve a greater than 3-log reduction in RU...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2013.02.010
更新日期:2013-07-01 00:00:00
abstract::Recent studies indicate that lipid metabolic changes affect the survival of multiple myeloma (MM) cells. Time-of-flight secondary ion mass spectrometry (TOF-SIMS), an imaging mass spectrometry technique, is used to visualize the subcellular distribution of biomolecules including lipids. We therefore applied this metho...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2015.02.011
更新日期:2015-06-01 00:00:00
abstract::Adult T-cell leukemia/lymphoma is a distinct clinical entity characterized by a clonal proliferation of malignant T-lymphocytes. The etiologic agent of the disease is a Human T-cell lymphotropic virus type I. It occurs almost exclusively in areas where the virus is endemic; however the disease develops only in the min...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.02.011
更新日期:2010-12-01 00:00:00
abstract::We determined the position of the breakpoint within the bcr gene in 22 patients with Philadelphia-positive chronic myelocytic leukemia using conventional Southern-blots and analyzed its relationship to thrombopoiesis. After DNA digestion with restriction endonucleases (Hind III, Bam HI and Bgl II), we localized the br...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(91)90113-8
更新日期:1991-01-01 00:00:00
abstract::Proliferative responses of mononuclear cells in liquid cultures to phytohemagglutinin, a T-cell mitogen, are depressed for a long time after allogeneic marrow transplantation. We examined the role of interleukin-2, a lymphokine important in T-cell mitogenesis, in the impaired phytohemagglutinin responses early after m...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(84)90081-x
更新日期:1984-01-01 00:00:00
abstract::Determination of T-cell clonality has an important additional value for diagnosis of T-cell lymphomas. Various molecular methods have been developed, including polymerase chain reaction (PCR) of T-cell receptor γ (TCRγ). The detection of PCR products usually relies commonly on either GeneScan (GS) analysis or heterodu...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2012.06.003
更新日期:2012-09-01 00:00:00
abstract::Testis-specific gene antigen (TSGA10) is expressed in fetus, testis and frequently in human solid cancers and acute leukemias, making it a candidate for immunotherapy and for detection of minimal residual disease (MRD). This gene is considered as a member of cancer-testis (CT) genes. We previously demonstrated TSGA10 ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.11.012
更新日期:2006-07-01 00:00:00
abstract::The efficiency of gene transfer into human leukemia cell lines by electroporation was investigated. For both transient expression (beta-galactosidase gene) and stable transformation (neomycin resistance gene), the transfer efficiency into leukemia cell lines using a square wave pulse was superior to that using an expo...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(91)90062-x
更新日期:1991-01-01 00:00:00
abstract::In 141 adult patients with diagnosis of acute myeloid leukemia the overall expression and intensity of expression of CD34 antigen on leukemic cells was investigated. Myeloid blasts were tested by applying direct immunofluorescence staining using anti-CD34 fluorescein monoclonal antibody in flow cytometry. CD34 antigen...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(97)00015-5
更新日期:1997-07-01 00:00:00
abstract::Chronic B-lymphocytic leukemia (B-CLL) cells may be regulated by immune functions. In an attempt to analyze such functions, helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8) and sIL-2R and beta 2-microglobulin were measured in serum of patients at different stages of the disease. Patient...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90009-v
更新日期:1992-06-01 00:00:00
abstract:BACKGROUND:Acute myeloid leukemia (AML) represents a heterogeneous disorder with recurrent chromosomal alterations and molecular abnormalities. Among AML with normal karyotype (NK-AML) FLT3 activating mutation, internal tandem duplication (FLT3-ITD), is present in about 30% of patients, conferring unfavorable outcome. ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2015.04.017
更新日期:2015-08-01 00:00:00
abstract::Experimental data are in keeping with the finding that megakaryocytes isolated from normal human bone marrow may promote fibroblast growth. This effect can be significantly enhanced by interleukin (IL)-3. In this context it has been demonstrated that IL-3 induces the release of platelet-derived growth factor (PDGF) an...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(99)00091-0
更新日期:1999-08-01 00:00:00
abstract::Chronic Lymphocytic Leukemia B cells (CLL) are malignant cells which retain at least some functions of normal B cells. Paramount amongst the latter is that when such cells are appropriately stimulated, they are able to present antigens, including any potential tumor antigens, making them excellent choices as a candida...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2018.03.002
更新日期:2018-05-01 00:00:00
abstract::Pro-apoptotic signalling upon toll-like receptor (TLR) stimulation in myeloid cells is normally antagonized by the simultaneous activation of anti-apoptotic pathways. We have previously reported that IFN-alpha can sensitize human monocytes to apoptosis induction by lipopolysaccharide (LPS). Based on these results we i...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.05.001
更新日期:2007-12-01 00:00:00
abstract::Protein tyrosine kinase-7 (PTK7) was recently identified as a surface protein expressed on hematopoietic cells. To determine if PTK7 is a useful biomarker in clinical practice for acute leukemia immunophenotyping and detection, we examined the PTK7 expression in human bone marrow and thymic specimens. Our results show...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2012.07.004
更新日期:2012-11-01 00:00:00
abstract::Human promyelocytic leukemia cells (HL-60) mature into functional granulocytes in response to in vitro treatment with several classes of chemical agents. Compounds that increase intracellular adenosine 3':5' -cyclic monophosphate induce a modified program of maturation in which the cells demonstrate functional propert...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(85)90311-x
更新日期:1985-01-01 00:00:00