Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trisomy 21 is the most common chromosomal abnormality among persons with intellectual disability, with a live birth rate of 1 in 800-1,000. As such, this abnormality may serve as a model for human disorders that result from supernumerary copies of a genomic region. Down syndrome carries an increased risk of developing acute leukemia and other malignancies. Telomeres of tumor cells nuclei tend to form aggregates (TA). This study evaluated TA formation in amniocytes from trisomy 21 pregnancies, compared with amniocytes from normal euploid pregnancies. A commercially available peptide nucleic acid telomere kit was used to evaluate TA formation, using two-dimensional fluorescence microscopy. Significantly higher frequencies of TA were found in trisomy 21 amniocytes than in amniocytes from normal pregnancies. The TAs found in trisomy 21 amniocytes apparently represent an additional parameter that reflects the high genetic instability of this syndrome and its recognized predisposition to develop leukemia and other malignancies.
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PMID:Telomere aggregates in trisomy 21 amniocytes. 1983 64

P-glycoprotein (P-gp, a drug transporter found in the plasma membrane)-mediated multidrug resistance of leukemia cells represents a real obstacle in the effective chemotherapeutic treatment of leukemia. While cisplatin (CisPt) is known to be a substance that is untransportable by P-gp, P-gp positive cells were often found to be resistant to CisPt. The aim of the current paper is to study this phenomenon using P-gp positive mouse leukemia cells L1210/VCR in which the overexpression of P-gp was induced by its ability to adapt to growth on vincristine (VCR). L1210/VCR cells are also resistant to CisPt. However, resistance to this substance could not be reversed by addition of the known P-gp inhibitor verapamil. CisPt induced more pronounced entry into apoptosis, as measured using the annexin V/propidium iodide kit, in sensitive L1210 cells than in resistant L1210/VCR cells. In addition, CisPt induced an increase in the proportion of L1210 cells that were in the g2 phase of the cell cycle when compared to L1210/VCR cells, as measured by staining with propidium iodide. Similarly, a higher release of cytochrome c from the mitochondria to the cytosol was induced by CisPt treatment in L1210 than in L1210/VCR cells. While similar levels of Bax and Bcl-2 proteins were observed in sensitive and resistant cells, CisPt induced a more pronounced decrease of the Bcl-2 levels in L1210 cells than in L1210/VCR cells. Consistent with this observation, CisPt induced a larger decrease of the Bcl-2 content in the Bcl-2:Bax heterooligomer in L1210 cells than in L1210/VCR cells. Moreover, CisPt induced a similar apoptotic DNA fragmentation pattern in both resistant and sensitive cells. All of the above observations indicated that L1210/VCR cells are also resistant to CisPt and that this resistance is related to the differences in the regulatory mechanisms responsible for CisPt-induced apoptosis in L1210/VCR cells without any contribution from the drug efflux activity of P-gp.
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PMID:Multidrug resistant P-glycoprotein positive L1210/VCR cells are also cross-resistant to cisplatin via a mechanism distinct from P-glycoprotein-mediated drug efflux activity. 2009 62

G-rich oligonucleotides (GROs) belong to a novel class of phosphodiester oligonucleotides. They can form G-tetramer structure which contributes to cell cycle arrest and growth inhibitory effects by non-antisense pathway. This study was aimed to investigate the biological effects of GRO-26B on leukemia cell lines. Cell proliferation of different cell lines were detected by using MTT method and trypan blue incorporation assay. Alteration of cell cycle was analyzed by using flow cytometry. Apoptosis was detected by using Annexin V/PI kit. Western blot was used to detect the expression level of cyclins and CDKs. Morphological features of GRO-26B-treated cells was observed by light microscopy and transmission electron microscopy (TEM). The results showed that GRO-26B could inhibit the proliferation of AML cell lines, such as U937 and NB4 cells in a dose-dependent manner. GRO-26B induced the cell cycle to be arrested at S phase in time-dependent manner, which was associated with the alteration of cyclin A, cyclin B, CDC2 and CDK2. The morphology of cells treated by GRO-26B also showed a distinct change as compared to the untreated cells. It is concluded that GRO-26B can inhibit AML cell proliferation, which is partially associated to cell cycle arrest at S phase. The S phase arrest is related to cyclins/CDKs. The regulation mechanism of cell cycle and proliferation is complicated. All of the above-mentioned phenomena need to be studied in the future.
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PMID:[Inhibition of leukemia cell proliferation by G-rich oligonucleotides]. 2013 12

We performed in vitro co-cultivation experiments with primary human nasal epithelial cells (HNEC) and isolated lymphocytes to investigate whether reactive formaldehyde (FA) can be passed on from nasal epithelial cells (site of first contact) to lymphocytes located in close proximity and induce DNA damage in these cells. A modified comet assay was used as a sensitive method for the detection of FA-induced DNA-protein cross links (DPX) because DPX are the most relevant type of FA-induced DNA damage. Our results clearly indicate that co-cultivation of lymphocytes with HNEC exposed to FA for 1 h causes a concentration-related induction of DPX in lymphocytes when co-cultivation takes place in the exposure medium. However, when the exposure medium is changed after FA treatment of HNEC and before lymphocytes are added, no induction of DPX is measured in lymphocytes even after exposure of HNEC to high FA concentrations (300 microM) and extended co-cultivation (4 h). Direct measurement of FA in the cell culture medium by a sensitive fluorescent detection kit indicated that FA is actually not released even from highly exposed cells into the cell culture medium. These results suggest that FA that has entered nasal epithelial cells is not released and does not damage other cells in close proximity to the epithelial cells. If these results also apply to the in vivo situation, FA would only be genotoxic towards directly exposed cells (site of first contact) and there should be no significant delivery of inhaled FA to other cells and distant sites. Our results do not support a recently proposed hypothetic mechanism for FA-induced leukaemia by damaging circulating haematopoietic stem cells or haematopoietic progenitor cells in nasal passages, which then travel to the bone marrow and become initiated leukaemic stem cells.
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PMID:Exposure of human nasal epithelial cells to formaldehyde does not lead to DNA damage in lymphocytes after co-cultivation. 2029 26

Different signaling routes seem to be simultaneously triggered in leukemia, with distinct and overlapping activities. Different reports emphasize the interaction between vascular endothelial growth factor (VEGF) and integrin alphavbeta3 as a key control system of angiogenesis, oncogenesis and metatasis. The current study was undertaken to investigate leukocytic-VEGF and integrin alphavbeta3 as correlated with clinical outcome in patients with acute myeloid leukemia (AML). The study groups included 10 newly diagnosed AML patients before the start of any chemotherapeutic medication and 10 normal healthy control subjects. The level of VEGF was estimated in culture supernatant of peripheral blood mononuclear cells (PBMN) of both groups using commercially available ELISA kit. The degree of integrin alphavbeta3 expression on PBMN was estimated by indirect immunoflourescence. Obtained results showed that the level of VEGF and degree of expression of integrin alphavbeta3 were significantly higher in AML patients than in normal healthy subjects. However, no significant correlation was observed between the levels of VEGF and the degree of expression of integrin alphavbeta3. When clinical findings were concerned, there was a significant positive correlation between VEGF and the percentage of blasts, both in peripheral blood & bone marrow. On the other hand, such correlations were not observed in case of integrin alphavbeta3. In addition no significant correlation was observed between either VEGF or integrin alphavbeta3 and clinical staging, age, and sex. In conclusion, our results proved the importance of VEGF and integrin alphavbeta3 in the pathogenesis of AML. However, the per se increased production or/and secretion of VEGF and integrin alphavbeta3 by leukemic PBMN cells, respectively can not be used as independent predictor (s) for clinical outcome in AML patients. It is more comprehensive to study changes of intracellular signaling pathways when such critically interacting factors are concerned in the leukemic process.
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PMID:Leukocytic-vascular endothelial growth factor and integrin alphavbeta3 in acute myeloid leukemia: relation to clinical outcome. 2030 91

This study was purposed to investigate the expression and role of eukaryotic expression vector containing p16, dll4 genes in leukemia K562 cells. A vector pBudCE4.1-16-dll4 containing wild type p16cDNA and dll4cDNA was designed and constructed, then this vector was transfected into leukemia K562 cells by using lipofectamine 2000. The expression of p16 and dll4 genes was detected by Western blot, the cell growth curve and cell cycle were determined by CCK-8 kit and flow cytometry respectively. The results showed that the recombinant plasmid pBudCE4.1-16-dll4 was constructed and transfected into K562 cells in vitro successfully. The expression of exogenous P16 and Dll4 proteins could be detected in K562 cells. After transfection for 48 hours, the K562 cells were arrested in G(1) phase, the cell count increased in G(0)/G(1) phase and reduced in S phase, the cell proliferation decreased as compared with control. It is concluded that the p16 and dll4 genes can simultaneously express in K562 cells transfected with recombinant plasmid pBudCE4.1-16-dll4 in vitro which results in G(0)/G(1) arrest and reduces cell proliferation.
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PMID:[Arresting effect of p16 and dll4 transfection on cell cycle of K562 cells]. 2056 7

Tanshinone I (Tan-I) is a diterpene quinone extracted from the traditional herbal medicine Salvia miltiorrhiza Bunge. Recently, Tan-I has been reported to have anti-tumor effects. In this study, we investigated the growth inhibition and apoptosis inducing effects of Tan-I on three kinds of monocytic leukemia cells (U937, THP-1 and SHI 1). Cell viability was measured by MTT assay. Cell apoptosis was assessed by flow cytometry (FCM) and AnnexinV/PI staining. Reverse transcriptase polymerase chain reaction (RT-PCR) and PCR-enzyme-linked immunosorbent assay (ELISA) were used to detect human telomerase reverse transcriptase (hTERT) expression and telomerase activity before and after apoptosis. The activity of caspase-3 was determined by Caspase colorimetric assay kit and Western blot analysis. Expression of the anti-apoptotic gene Survivin was assayed by Western blot and Real-time RT-PCR using the ABI PRISM 7500 Sequence Detection System. The results revealed that Tan-I could inhibit the growth of these three kinds of leukemia cells and cause apoptosis in a time- and dose-dependent manner. After treatment by Tan-I for 48 h, Western blotting showed cleavage of the caspase-3 zymogen protein with the appearance of its 17-kD subunit, and a 89-kD cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also found clearly. The expression of hTERT mRNA as well as activity of telomerase were decreased concurrently in a dose-dependent manner. Moreover, Real-time RT-PCR and Western blot revealed a significant down-regulation of Survivin. We therefore conclude that the induction of apoptosis by Tan-I in monocytic leukemia U937 THP-1 and SHI 1 cells is highly correlated with activation of caspase-3 and decreasing of hTERT mRNA expression and telomerase activity as well as down-regulation of Survivin expression. To our knowledge, this is the first report about the effects of Tan-I on monocytic leukemia cells.
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PMID:Down-regulation of telomerase activity and activation of caspase-3 are responsible for Tanshinone I-induced apoptosis in monocyte leukemia cells in vitro. 2064 Jan 51

We investigated the priming effect and mechanism of granulocyte colony-stimulating factor (G-CSF) in chemotherapy with low-dose Ara-C and VP-16 for acute myeloid leukemia. We analyzed cell proliferation, apoptosis, and cell cycle in vitro using leukemia cell lines 32Dcl3, U937, HL-60, and Ba/F3. Cell proliferation assays were performed using the Trypan Blue dye exclusion method. For detection of apoptosis, the Annexin V-binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used an FITC BrdU Flow kit and conducted analysis by flow cytometry. The combination of Ara-C and VP-16 significantly enhanced the observed effects compared with those of Ara-C or VP-16 alone. Concurrent administration of G-CSF further reduced the cell number and viability of 32Dcl3 and U937 cells, but not of HL-60 and Ba/F3 cells. Apoptotic cells were significantly increased in number by the addition of G-CSF to 32Dcl3 and U937 cells, while G-CSF had no significant effect on HL-60 and Ba/F3 cell lines. The addition of G-CSF significantly decreased the percentage of G0/G1-phase cells and significantly increased that of S-phase cells among 32Dcl3 and U937 cells. No significant effect was observed for HL-60 and Ba/F3 cells. An enhancement was confirmed for the combination of Ara-C, VP-16, and G-CSF for 32Dcl3 and U937 cells but not for HL-60 and Ba/F3 cells. It was thought that this difference was a result of different responses to G-CSF. G-CSF potentiates Ara-C- and VP-16-induced cytotoxicities through apoptosis induction by mobilizing resting G0-G1-phase cells into S phase.
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PMID:Cell cycle-dependent priming action of granulocyte colony-stimulating factor (G-CSF) enhances in vitro apoptosis induction by cytarabine and etoposide in leukemia cell lines. 2112 67

During pilot studies to investigate the presence of viral RNA of xenotropic murine leukemia virus (MLV)-related virus (XMRV) infection in sera from chronic fatigue syndrome (CFS) patients in Japan, a positive band was frequently detected at the expected product size in negative control samples when detecting a partial gag region of XMRV using a one-step RT-PCR kit. We suspected that the kit itself might have been contaminated with small traces of endogenous MLV genome or XMRV and attempted to evaluate the quality of the kit in two independent laboratories. We purchased four one-step RT-PCR kits from Invitrogen, TaKaRa, Promega and QIAGEN in Japan. To amplify the partial gag gene of XMRV or other MLV-related viruses, primer sets (419F and 1154R, and GAG-I-F and GAG-I-R) which have been widely used in XMRV studies were employed. The nucleotide sequences of the amplicons were determined and compared with deposited sequences of a polytropic endogenous MLV (PmERV), XMRV and endogenous MLV-related viruses derived from CFS patients. We found that the enzyme mixtures of the one-step RT-PCR kit from Invitrogen were contaminated with RNA derived from PmERV. The nucleotide sequence of a partial gag region of the contaminant amplified by RT-PCR was nearly identical (99.4% identity) to a PmERV on chromosome 7 and highly similar (96.9 to 97.6%) to recently identified MLV-like viruses derived from CFS patients. We also determined the nucleotide sequence of a partial env region of the contaminant and found that it was almost identical (99.6%) to the PmERV. In the investigation of XMRV infection in patients of CFS and prostate cancer, researchers should prudently evaluate the test kits for the presence of endogenous MLV as well as XMRV genomes prior to PCR and RT-PCR tests.
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PMID:An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR kit is amplified using standard primers for XMRV. 2117 78

This study was purposed to detect single nucleotide polymorphisms (SNP) of 2 pharmacokinetics-related genes in K562 and K562/A02 cell lines. Leukemia cell line K562 and its resistant line K562/A02 were cultured, the genomic DNA was isolated by QIAamp DNA Blood Mini kit, primers were designed, the related DNA fragments were amplified by PCR. The SNP genotyping of mthfr gene rs1801131, rs1801133 and rs2274976 and dpyd gene rs1801159, rs1801160 and rs17376848 was performed by means of matrix assisted laser desorption ionization-time of flight mass spectrometry method (MALDI-TOFMS). The results showed that the genotype of mthfr gene locus 1801131 was AC, rs1801133 was CC, rs2274976 was GG, genotype of dpyd gene locus 1801159 was GG, rs1801160 was GG, rs17376848 was AA in both K562 and K562/A02 cell lines. It is concluded that the above-mentioned loci of mthfr and dpyd genes in K562 and K562/A02 cell lines are not expressed differently.
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PMID:[Detection of single nucleotide polymorphisms of mthfr and dpyd genes in leukemia cell lines K562 and K562/A02]. 2136 12


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