Summary
Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying these early transcription events is largely unknown. We demonstrate that several IEGs such as arc/arg3.1 are poised for near-instantaneous transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site in rat neurons. RNAi-depletion of Negative Elongation Factor, a mediator of Pol II stalling, reduces the Pol II occupancy of the arc promoter and compromises the rapid induction of arc and other IEGs. In contrast, reduction of Pol II stalling did not prevent transcription of IEGs that are expressed later and largely lack promoter proximal Pol II stalling. Together, our data strongly indicate that rapid induction of neuronal IEGs requires poised Pol II and suggest a role for this mechanism in a wide variety of transcription-dependent processes, including learning and memory.
Summary. The aim of this study was to evaluate the outcomes for Philadelphia‐chromosome‐positive acute lymphoblastic leukaemia (Ph+ ALL) patients in remission treated with allogeneic bone marrow transplantation (BMT). Twenty‐three adults were entered onto this study. The 2‐year probabilities of relapse and disease‐free survival (DFS) were 39·4 ± 11·6% and 43·5 ± 10·3% respectively. The presence of chronic graft‐versus‐host disease (GVHD) was found to be an independent predictive factor affecting lower relapse and DFS. To monitor the BCR‐ABL transcript, we also analysed 48 bone marrow samples of eight patients using real‐time quantitative reverse‐transcription polymerase chain reaction (RT‐PCR). The kinetics of the BCR‐ABL transcript correlated well with the patients' clinical course. In six patients who were in continuous remission after BMT, a rapid decrease in BCR‐ABL copy number to the PCR‐negative status was observed after the development of chronic GVHD. Meanwhile, routine bone marrow examination of two patients showed PCR positivity with a 3 or 4‐log increase of BCR‐ABL copy number and subsequent haematological relapse, which occurred 2 and 4 months later respectively. Although our data should be interpreted cautiously, the presence of chronic GVHD may reduce the risk of relapse in Ph+ ALL. Real‐time quantitative RT‐PCR appears to be a useful test for BCR‐ABL transcript monitoring.
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