Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hierarchical level of stem cell involvement in acute promyelocytic leukemia (APL) characterized by the pathognomonic PML-RARA fusion gene is unknown. To determine if the cells of the primitive hematopoietic stem cell compartment are involved in the leukemic process, we have used molecular and cell sorting techniques in peripheral blood and bone marrow (BM) cells at diagnosis from three patients with APL and t(15; 17). In two of them, clonality analysis was also possible using the BstXI polymorphic site of the PGK gene. The PML-RARA fusion gene was readily identified by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of BM cells obtained at diagnosis in all three patients. These same samples were then used to sort CD34+ cells and their CD38+ and CD38- subsets by fluorescence-activated cell sorting. In both female patients, CD34+/CD38+ and CD34+/CD38- cell fractions were polyclonal using PCR, whereas a monoclonal pattern was identified at the BM sample obtained at diagnosis either by Southern blotting or by PCR. Because of the high sensitivity of the PCR analysis, the polyclonal pattern of these cell populations could mask the presence of a minor clone. To detect this clone, we preformed RT-PCR analysis for t(15; 17). In one female patient, the abnormal PML-RAR fusion gene was found only in the more mature CD34+/CD38+ cell fraction using a nested PCR approach, whereas the polyclonal CD34+/CD38- fraction was PML-RARA negative. These findings were confirmed in a third patient with APL in whom the PML-RARA transcripts were absent in the CD34+/CD38- cell fraction. To study the clonality at the level of clonogenic progenitors, we used in one patient PGK analysis by PCR of individual burst-forming units-erythroid and colony-forming units-granulocyte-macrophage obtained from the CD34+/CD38- and CD34+/CD38+ cell populations at diagnosis and from the BM sample obtained during remission. The two highly purified cell populations gave rise to morphologically normal colonies clonal for both the BstXI site containing (A) and the BstXI site lacking (B) PGK allelles, indicating their polyclonal content, a pattern that was also found in clonogenic progenitors obtained at remission. These findings strongly suggest that the primitive hematopoietic stem cells as defined by the CD34+/CD38- antigens are not involved by the neoplastic process in APL. These results may have important implications for autografting strategies of retinoic acid/chemotherapy-resistant or relapsed patients.
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PMID:Highly purified primitive hematopoietic stem cells are PML-RARA negative and generate nonclonal progenitors in acute promyelocytic leukemia. 753 93

Neurotrophins are known to influence Schwann cells during development and to promote peripheral nerve regeneration after axonal damage. In neoplastic conditions. Schwann cells from experimentally-induced schwannomas appear to retain their responsiveness to nerve growth factor (NGF), although the role of neurotrophins in the neoplastic process in poorly understood. In this study, human neoplastic Schwann cells (five cases of acoustic schwannoma and two cases of malignant peripheral nerve sheath tumours [MPNST]) were investigated for the expression in situ of molecules of the neurotrophin system. In particular, we studied the 75 kDa low-affinity receptor (p75) and the mRNA for its ligands, NGF and neurotrophin-3 (NT-3). By immunohistochemistry, the p75 receptor was found to be the present at high levels in Schwann cells from acoustic schwannomas, whereas it was very weak or absent in MPNST. Messenger RNA for NGF and NT-3 was detected by reverse transcriptase in situ polymerase chain reaction technique and showed the same fluctuation of p75, being up-regulated in acoustic schwannomas and very weak or absent in MPNST. In normal non-neoplastic tissue, no detectable amounts of either ligand or receptor were observed. Our results indicate that changes in the expression of neurotrophins and their p75 receptor occurred during the neoplastic transformation of Schwann cells. In benign schwannomas, such changes are likely to reflect the loss of axonal contact, while in MPNST they may be related to a complete derangement of cell machinery in the tumour cells.
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PMID:Human neoplastic Schwann cells: changes in the expression of neurotrophins and their low-affinity receptor p75. 936 63

We investigated the utility of noninvasive technology utilizing feces containing exfoliated colonocytes to determine whether changes in fecal fatty acid-binding proteins have predictive value in monitoring the neoplastic process. Ninety male Sprague-Dawley rats were randomly divided into four groups in a 2 x 2 factorial design, with two dietary fiber sources (wheat bran or oat bran) and two treatment groups (injection with a carcinogen, azoxymethane, or saline). Fresh fecal samples were collected at Week 16 postinjection, and tumor frequency was determined at Week 36 of the study. Semiquantitative "mimic" reverse transcriptase polymerase chain reaction was used to quantitate the expression of liver fatty acid-binding protein (L-FABP), intestinal fatty acid-binding protein (i-FABP), and acyl CoA-binding protein (ACBP) mRNA in fecal samples to establish their prognostic value. Rats fed wheat bran diets had a lower incidence of tumors (p < 0.05). There was no effect of carcinogen injection or tumor incidence on the expression of L-FABP, i-FABP, or ACBP mRNA, L-FABP and i-FABP mRNA expression were significantly higher (p < 0.05) in feces from animals fed a wheat bran diet than in feces from animals fed an oat bran diet. In contrast, the expression of ACBP mRNA was significantly lower (p < 0.05) in animals fed a wheat bran diet than in animals fed an oat bran diet. Wheat bran also increased (p < 0.05) the total excretion of L-FABP, i-FABP, and ACBP over a 48-hour period. These data suggest that exfoliated colonocyte fatty acid-binding protein mRNA status may provide insight into the mechanisms by which diet influences colonic physiology.
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PMID:Dietary fiber differentially alters cellular fatty acid-binding protein expression in exfoliated colonocytes during tumor development. 991 20

The progressive shortening of telomeres at each cell division is a key mechanism in controlling cell proliferative capacity. The activation of telomerase, a reverse transcriptase that extends telomere length, potentially leads to unlimited cell proliferation, and is believed to play a critical role in the neoplastic process. High levels of telomerase activity have been demonstrated in almost all solid tumours; however, little data is available concerning its expression in chronic B-cell neoplasms. By using a quantitative polymerase chain reaction-based method we quantified telomerase activity in normal B lymphocytes, and in various B-cell malignancies, including chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL) and hairy cell leukaemia (HCL). Compared to normal B cells, which expressed very low levels of telomerase activity, malignant cells from most of the patients showed a significant increase in telomerase activity, with highest values observed in HCL samples. Moreover, among the CLL and HCL cases, significantly higher levels of telomerase activity were found in patients with progressive disease at 1 year follow-up versus patients with stable disease. These data suggest that telomerase activity might correlate with disease progression.
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PMID:Telomerase activity in chronic lymphoproliferative disorders of B-cell lineage. 1046 54