We reported recently that cobalt chloride-simulated hypoxia and mild hypoxia modified the differentiation of human acute myeloid leukemic (AML) cells, probably acting via a hypoxiainducible factor-1 alpha (HIF-1a)-dependent mechanism. In this study, we investigated the effect of desferrioxamine (DFO), an iron chelator with 'hypoxia-mimetic' activity, on the differentiation of AML cells. The results showed that DFO at nontoxic concentrations induced the differentiation of AML cell lines NB4 and U937, as assessed by morphological criteria and differentiation-associated antigens. DFO-induced differentiation parallel to the rapid accumulation of HIF-1a protein in these two cell lines. Of importance, the transient transfection of HIF-1a cDNA induced U937 cells to develop the differentiationrelated alterations such as growth arrest and increased CD11b expression. Furthermore, the inducible expression of chromosome translocation t(8;21)-generated leukemogenic AML1-ETO fusion gene attenuated DFO-induced differentiation of U937 cells with the decrease of CCAAT/enhancer-binding protein alpha (C/EBPa), a critical factor for granulocytic differentiation. Using immunoprecipitation and luciferase reporter assay, HIF1a was also shown to interact physically with and to increase the transcriptional activity of C/EBPa. Taken together, these results provided novel evidence for a role of HIF-1a in AML cell differentiation, and suggested that C/EBPa might be a downstream effector for HIF-1a-mediated differentiation.

Leukemia-associated fusion protein AML1-ETO is a product of the chromosome translocation (8;21) frequently occurred in acute myeloid leukemia (AML). The fusion oncoprotein blocks leukemic cell differentiation, and it also induces growth arrest with increased sensitivity to apoptosis induction. Such dichotomous functions make it difficult to clarify the role of AML1-ETO in leukemogenesis. Here, we systematically showed that constitutively and overexpressed AML1-ETO protein was cleaved to four fragments of 70, 49, 40 and 25 kDa by activated caspase-3 during apoptosis induction by extrinsic mitochondrial and death receptor signaling pathways. The in vitro proteolytic system combined with MALDI-TOF/TOF mass spectrometer confirmed that AML1-ETO and wild-type ETO but not RUNX1 (AML1) proteins were direct substrates of apoptosis executioner caspase-3. Site-directed mutagenesis analyses identified two nonclassical aspartates (TMPD 188 and LLLD 368 ) as caspase-3-targeted sites in the AML1-ETO sequence. When these two aspartates were mutated into alanines, more intriguingly, the apoptosis-amplified action of AML1-ETO induction completely disappeared, while inducible expression of the caspase-3-cleaved 70 kDa fragment of AML1-ETO after tetracycline removal is sufficient to enhance apoptotic sensitivity. Further investigations on the potential in vivo effects of such a cleavage and its possible role in leukemogenesis would provide new insights for understanding the biology and treatment of AML1-ETO-associated leukemia.

Objective: The purpose of this study was to assess radio frequency (RF) artefacts in echoplanar imaging (EPI) induced by two 1.5T MR scanners in close proximity and to find an effective method to correct them. Methods: Based on the intact shielding of rooms, experiments were performed by two MR scanners with similar centre frequencies. Phantom A (PA) was scanned in one scanner by EPI at different bandwidths (BWs). Simultaneously, phantom B was scanned in a fixed sequence for scanning with the other scanner. RF artefact gaps of PA, scanning time and the image signal-noise ratio (SNR) were measured and recorded. Statistical analysis was performed with the repeatedmeasures analysis of variance test. Based on findings obtained from PA, three healthy volunteers were studied at a conventional BW and a lower BW to observe the artefact variance. Results: EPI RF artefacts were symmetrically situated in both sides of the image following the phase-encoding direction. The gap size of the artefact became larger and the SNR was significantly improved with a narrower BW. RF artefacts with a lower BW in volunteers presented the same characteristic as PA. Conclusion: For EPI RF artefacts produced by two 1.5 T MR scannerswithapproximatelysimilarcentrefrequencies,wecan reduce BWs in a suitable range to minimize the effect on MRI. Advances in knowledge: MR scanners with the same field strength installed in the same vicinity might produce RF artefacts in the sequence at larger BWs. Reducing BWs properly is effective to control the position of artefacts and improve the image quality.Owing to the limited space and inappropriate planning, two 1.5 T MR scanners in our hospital were installed with their apertures facing each other at the same level. Subsequently, artefacts appeared in MR images when they were used at the same time. Artefacts that severely impaired the quality of MR images were a band or zipper of intensity perpendicular to the frequency-encoding direction. They frequently appeared in many conventional sequences, so that the scanning could not work. We and the engineers studied the characteristics of the artefacts and considered them radiofrequency (RF) artefacts. We tried our best to search for the interference source, but we could not be sure what instrument it came from. After recording and analysing artefacts, we found an apparent law. Only when two scanners were used at the same time did the RF artefacts appear in many sequences. After closing the RF coil of one scanner, RF artefacts disappeared from the images of the other. Therefore, we considered that these artefacts were produced from the interaction between two scanners. Two MR scanners have the same field strength of 1.5 T and a similar approximate centre frequency (Avanto 5 63.680982 MHz; Symphony 5 63.685914 MHz). The difference of the centre frequencies between both scanners is 4932 Hz. As soon as half of the sampling rate of the sequence is .4932 Hz, RF of the opposite scanner will be received and fill in the k-space corresponding to the frequency range whe...