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)

Continuous cell lines are frequently contaminated with microorganisms, mycoplasmas being the most prominent and cumbersome. In our experience, of the 300 cell lines examined more than one third was infected with mycoplasmas. Mycoplasma contamination can affect virtually every parameter and functional activity of a cultured cell. An alternative to the recommended disposal of infected cultures is an attempt to eliminate the contaminants. Adding antibiotics with strong activity against mycoplasmas to the culture medium is a simple, inexpensive and efficient decontamination method. Here, we studied the effectiveness of the new antibiotic enrofloxacin (Baytril) developed specifically for use against mycoplasmas. Baytril is a new synthetic agent from the group of quinolone derivatives that are DNA gyrase inhibitors. Thirty-two chronically infected cell lines (27 human leukemia-lymphoma cell lines) were treated with Baytril in a prospective study in direct comparison with three other well-established anti-mycoplasma regimens, the antibiotics BM-Cyclin, Ciprobay and MRA (Mycoplasma Removal Agent). Mycoplasmas were detected by DNA staining, agar colony growth, DNA-RNA hybridization, polymerase chain reaction, and monoclonal antibody staining. Treatment with Baytril eliminated the contaminants in 30/32 cultures (94%). The cure rates for Ciprobay, BM-Cyclin and MRA were 91%, 81%, and 75%, respectively. The IC50 values of Baytril for cell lines varied over a wide range depending on the type of hematopoietic cell lineage with T- and B-cell lines being more sensitive targets. Baytril-treated cell lines remained mycoplasma-negative over a 12-week antibiotic-free culture period. Low levels of mycoplasma infection were shown not to persist by repeat testing after growth without antibiotics. A retrospective analysis of anti-mycoplasma treatments with BM-Cyclin, Ciprobay, MRA or Baytril showed that 265/351 cultures (75%) were immediately cured of mycoplasma; however, all of the remaining, mycoplasma-positive cultures harboring mycoplasms resistant to the first antibiotic could be cleaned up by a second round with a different antibiotic. Baytril is an efficient anti-mycoplasma antibiotic and based on its high cure rate might be the treatment of first choice.
Leukemia 1994 Aug
PMID:Effective treatment of mycoplasma contamination in cell lines with enrofloxacin (Baytril). 752 Jan 3

The expression of E and D-type cyclins, Cyclin-Dependent Kinase (CDK) 2 and 4, as well as CDK inhibitors p21Cip1 and p27Kip1 were examined during in vitro differentiation of mouse embryonic stem (ES) cells. ES cells cultured in presence of Differentiation Inhibitory Activity/Leukemia Inhibitory Factor (DIA/LIF) express very low levels of cyclin E/CDK2 complexes, p21Cip1 and p27Kip1 CDK inhibitors, while cyclin D/CDK4-associated kinase activity is undetectable. Withdrawal of DIA/LIF, which induces differentiation, results in the progressive up-regulation of all. Up-regulation of D cyclins occurs through an increase in the steady-state levels of mRNA, concomitantly with the activation of Brachyury and Goosecoid, two early markers of mesoderm differentiation. Similarly, cells from the epiblast of the early postimplantation mouse embryo do not express any cyclin D/CDK4 complexes. These are progressively upregulated at gastrulation and early organogenesis. DIA/LIF-stimulated ES cells are not growth-arrested by overexpression of p16Ink4a, a specific inhibitor of CDK4 and CDK6. We propose that the G1/S transition may be regulated by a minimal mechanism in mouse embryonic stem cells. Induction of differentiation triggers the establishment of a more sophisticated mechanism involving both cyclin D/CDK4- and CDK inhibitor-associated control of G1-phase progression.
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PMID:Withdrawal of differentiation inhibitory activity/leukemia inhibitory factor up-regulates D-type cyclins and cyclin-dependent kinase inhibitors in mouse embryonic stem cells. 857 Feb 8

Cyclin A is a cell cycle regulatory protein that functions in mitotic and S phase control in mammalian cells. However, in contrast to other G1 phase regulatory proteins, such as cyclin D, retinoblastoma protein and p16INK4A, cyclin A seems not to be commonly involved in tumorigenesis. Recently, a second human cyclin A--cyclin A1--has been identified. In contrast to cyclin A which is expressed throughout embryonic development and in adult tissue, the expression of cyclin A1 has been reported to be restricted to embryonic and germ line cells. We have confirmed the absence of cyclin A1 mRNA from normal peripheral blood leukocytes of seven healthy donors by single step reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, we have examined the expression of cyclin A1 mRNA in 173 peripheral blood samples of 162 patients with various hematological malignancies. Cyclin A1 mRNA was detectable in 11 of 11 patients with acute myeloid leukemia, three of three patients with acute biphenotypic leukemia, eight of eight patients with myelodysplastic syndrome, 59 of 69 patients with chronic myelogenous leukemia (CML) at diagnosis, 13 of 15 patients with CML in blastic transformation, 10 of 18 patients with chronic lymphocytic leukemia, two of nine patients with essential thrombocythemia, and only two of 10 patients with acute lymphoblastic leukemia (ALL) with both cyclin A1 RT-PCR positive ALL leukemias being undifferentiated relapses. In addition, cyclin A1 mRNA was found in one of six leukapheresis products, harvested from individuals without hematological disorders. Taken together, cyclin A1 is expressed in the majority of myeloid and undifferentiated hematological malignancies as well as in normal hematopoietic progenitor cells. We conclude that cyclin A1, a protein potentially involved in G1/S phase progression of immature cells, might be necessary for proliferation of early hematopoietic progenitor cells and their leukemic counterparts being blocked at that stage of differentiation.
Leukemia 1998 Jun
PMID:Cyclin A1 is predominantly expressed in hematological malignancies with myeloid differentiation. 963 17

Cyclin D1 participates in cell-cycle control, in the progression through the G(1) phase and in the transition from the G(1) to the S phase. The CCND1 locus, located in 11q13, is amplified and cyclin-D1 protein is over-expressed in a wide range of human solid tumors. In some B-lymphoid malignancies, the t(11;14)(q13;q32) translocation joins the Ig heavy-chain locus to the CCND1 locus and leads to cyclin-D1 over-expression. In this study, a series of 127 patients presenting a B-chronic lymphoproliferative disorder (B-CLPD) was analyzed using a competitive RT-PCR designed to detect cyclin-D1-mRNA over-expression. Cyclin-D1 mRNA was expressed in patients with mantle-cell lymphoma (MCL; 10/10), hairy-cell leukemia (HCL; 3/5), B-chronic lymphoid leukemia (B-CLL; 4/111) and B large-cell lymphoma (BLCL; 1/1). Densitometric analysis of RT-PCR products and Western-blot autoradiograms, in addition to cytogenetic data, indicated that activation of the cyclin-D1 gene occurred independently of the t(11;14)(q13;q32) translocation in patients with HCL. Indeed, a normal-sized protein of 36 kDa exhibiting a level incompatible with gene activation by a translocation mechanism was detected in lymphoid cells with a normal karyotype. Moreover, we found a discrepancy between cyclin-D1 mRNA and protein levels in MCL and B-CLL, which suggested that some regulatory mechanisms acting at a post-transcriptional level persist in tumor cells.
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PMID:Transcriptional and post-transcriptional mechanisms induce cyclin-D1 over-expression in B-chronic lymphoproliferative disorders. 1047 32

In this study subcellular localization of cyclin A in the human promyelocytic leukemia cell line HL-60 and the human erythroleukemic K-562 cell line was examined by immunocytochemical methods. Studies were based on light and electron microscope evaluations. Cyclin A at the level of light microscope was present in 48% of the cells in HL-60 cell line and in 40% of the cells in K-562 line. Streptavidin-gold method was used for localization of cyclin A at the ultrastructural level. There was expression of cyclin A in the nucleus and in the cytoplasm. In the nucleus gold particles were seen to be associated with the condensed chromatin of the both leukemia cell lines. In the cytoplasm cyclin A was concentrated at a low level and was associated with ribosomes. Controls of the leukemia cells incubated with normal mouse serum showed no labeling at the light and electron microscope level.
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PMID:Expression of cyclin A in human leukemia cell lines HL-60 and K-562 at the level of light and electron microscope by using immunocytochemical methods. 1147 90

Uncontrolled cell proliferation is the basic feature of cancer. Some of the prime cell cycle regulators are involved directly in tumorigenesis. Cyclin A, one of the G(1)/S cyclin, can cause transformation. The purpose of this research was to investigate whether cyclin A overexpression was involved in leukemogenesis and proliferation of leukemia cells. The expression of cyclin A at S-phase in leukemia cell line HL-60, blast cells of acute leukemia patients, bone marrow cells of outpatients without malignant hematological disease and peripheral blood cells of healthy donors was investigated by simultaneous indirect immunofluorescence staining of intracellular antigen and DNA. To further investigate whether cyclin A played as a key molecular in cell proliferation, HL-60 cells were exposed to different concentrations of hexamethylene bisacetamide (HMBA). MTT dye absorbance of living cells and cell cycle analysis were adopted to evaluate growth arrest. Differentiation was evaluated by detection of the change of expression of CD11b and CD33 on cell surface. The results showed that overexpression of cyclin A was only found among specimens from acute leukemia and leukemia cell line. There was no elevated cyclin A detection for cyclin A among specimens from outpatients and healthy donors. In HMBA interference experiment, HMBA was able to induce growth arrest and monocytic macrophage differentiation of HL-60 cells in a dose-dependent manner, and all these changes were associated with a marked down-regulation of cyclin A expression. In conclusion, aberrant overexpression of cyclin A at S-phase was only found in leukemia cell lines and blast cells from acute leukemia. The dose-dependent effect of HMBA on cell growth and differentiation of HL-60 cell line which was consistent with the decrease of cyclin A expression in these cells suggested that the molecular mechanisms of HMBA inducement involved downregulation of cyclin A expression.
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PMID:Clinical and laboratory studies of expression of cyclin A in leukemia cells. 1274 36

Cyclin A (A2) and cyclin A1 are members of the G2 cyclins, which are involved in the control of G2/M and G1/S transitions as well as mitosis. Human cyclin A1 was cloned as an A-type cyclin that is highly expressed in acute myeloid leukaemia (AML). The clinical significance of these cyclins in myeloid leukaemia remains to be clarified. We investigated the relative levels of these transcripts in 80 patients with de novo AML. Correlations with clinical parameters showed that the initial white blood cell count and serum lactate dehydrogenase levels were inversely associated with cyclin A (A2) mRNA levels (r = -0.276, P = 0.019) and cyclin A1 mRNA levels (r = -0.241, P = 0.042) respectively. They were independently associated with increased overall survival [P = 0.035 for cyclin A (A2) and P = 0.016 for cyclin A1]. Multivariate analysis using Cox's proportional hazard model showed that elevated cyclin A1 mRNA levels contributed significantly to the better prognosis of patients with AML. Furthermore, the analysis of survival probability showed that the group with high levels of both cyclin A (A2) and A1 survived significantly longer than the group with low expression of both these cyclins (P = 0.002). These data indicate that high expression levels of both cyclin A (A2) and A1 are associated with good prognosis in AML patients.
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PMID:Elevated levels of cyclin A1 and A (A2) mRNA in acute myeloid leukaemia are associated with increased survival. 1451 Sep 45

Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the anti-viral effects of PCIs have also been observed against various viruses, including human immunodeficiency virus (HIV), herpes simplex virus, and murine leukemia virus. Through the inhibition of CDK2 and 9, the cellular co-factors for HIV-1 Tat transactivation, HIV-1 replication is blocked by two specific PCIs, CYC202 and flavopiridol, respectively. In this article, we will review the inhibitory mechanisms of flavopiridol and CYC202 and discuss their possible usage in AIDS treatment.
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PMID:Potential use of pharmacological cyclin-dependent kinase inhibitors as anti-HIV therapeutics. 1678 40

Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated Taspase1(-/-) mice. Taspase1 deficiency results in noncleavage (nc) of MLL and MLL2 and homeotic transformations. Remarkably, our in vivo studies uncover an unexpected role of Taspase1 in the cell cycle. Taspase1(-/-) animals are smaller in size. Taspase1(-/-) mouse embryonic fibroblasts (MEFs) exhibit impaired proliferation, and acute deletion of Taspase1 leads to a marked reduction of thymocytes. Taspase1 deficiency incurs down-regulation of Cyclin Es, As, and Bs and up-regulation of p16(Ink4a) . We show that MLL and MLL2 directly target E2Fs for Cyclin expression. The uncleaved precursor MLL displays a reduced histone H3 methyl transferase activity in vitro. Accordingly, chromatin immunoprecipitation assays demonstrate a markedly decreased histone H3 K4 trimethylation at Cyclin E1 and E2 genes in Taspase1(-/-) cells. Furthermore, MLL(nc/nc;2nc/nc) MEFs are also impaired in proliferation. Our data are consistent with a model in which precursor MLLs, activated by Taspase1, target to Cyclins through E2Fs to methylate histone H3 at K4, leading to activation. Lastly, Taspase1(-/-) cells are resistant to oncogenic transformation, and Taspase1 is overexpressed in many cancer cell lines. Thus, Taspase1 may serve as a target for cancer therapeutics.
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PMID:Proteolysis of MLL family proteins is essential for taspase1-orchestrated cell cycle progression. 1695 Dec 54

Cyclin A(2) plays critical role in DNA replication, transcription, and cell cycle regulation. Its overexpression has been detected and related to many types of cancers including leukemia, suggesting that suppression of cyclin A(2) would be an attractive strategy to prevent tumor progression. Herein, we apply functionalized single wall carbon nanotubes (f-SWNTs) to carry small interfering RNA (siRNA) into K562 cells and determine whether inhibition of cyclin A(2) would be a potential therapeutic target for chronic myelogenous leukemia. The results show functionalized SWNTs can facilitate the coupling of siRNA specifically targeting human cyclin A(2) to form cyclin A(2) siRNA-f-SWNTs complexes. These functionalized SWNTs readily enter K562 cells, resulting in suppression of cyclin A(2) expression. We demonstrate that depletion of cyclin A(2) in this manner inhibits cell proliferation and promotes apoptosis, and cyclin A(2) can serve as a novel therapeutic target. siRNA against cyclin A(2) delivered by functionalized single wall carbon nanotubes may be a useful therapeutic strategy for chronic myelogenous leukemia cells. This would provide new insights on additional therapeutic options for chronic myelogenous leukemia beyond chemotherapy in light of increasing multidrug resistance.
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PMID:Targeted RNA interference of cyclin A2 mediated by functionalized single-walled carbon nanotubes induces proliferation arrest and apoptosis in chronic myelogenous leukemia K562 cells. 1828 53


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