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The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-alpha fusion messenger RNA species that can be detected by reverse transcription-polymerase chain reaction (RT-PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-alpha isoform, whereas breakpoints within intron 6 result in a longer form. Using RT-PCR, serial evaluations were performed on the bone marrow of 82 patients with APL (median follow-up, > 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. Sixty-four patients attained a clinical complete remission and had at least 2 RT-PCR assays performed after completing therapy. Forty of 47 patients (85%) with newly diagnosed APL who were induced using RA had residual disease detectable by RT-PCR before additional therapy. After 3 cycles of consolidation therapy, residual disease was found in only 4 of 40 evaluable patients (10%). Among newly diagnosed patients who had 2 or more negative RT-PCR assays, only 3 of 41 (7%) had a relapse, whereas all 4 patients (100%) who had 2 or more positive results had a relapse. Among 63 newly diagnosed patients, those who expressed the short isoform appeared to have shorter disease-free and overall survival durations than patients who expressed the long isoform. These data indicate that 2 or more negative RT-PCR assays on bone marrow, performed at least 1 month apart after completing therapy, are strongly associated with long-term remissions. Conversely, a confirmed positive test is highly predictive of relapse.
Acute promyelocytic leukemia (APL) is characterized cytogenetically by the t(15;17)(q22;q11-21) translocation. To compare molecular events among pediatric and adult APL cases, we designed two sets of oligonucleotide primers using published cDNA sequence for PML/RAR alpha fusion transcripts, and undertook reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 22 US pediatric cases of APL. PML/RAR alpha fusion transcripts were detected in all APL cases, including two cases lacking cytogenetic evidence of t(15;17). Breakpoint usage in PML was determined using a combination of PCR amplification with differing 5' primers, junction-specific probes, and sequence analysis in selected cases. Consistent with previously published data, case analysis demonstrated fusion products resulting from three breakpoint cluster regions (bcr) in PML, and a single breakpoint region in intron 2 of RAR alpha. Transcripts resulting from breakpoints in bcr1 were detected in 59 percent of cases, bcr2 in 27 percent and bcr3 in 14 percent. This distribution is dissimilar to that observed in adults, where bcr2 comprises a lesser and bcr3 a greater portion of cases. These results suggest that the pathogenesis of the t(15;17) in APL may differ among patient sets. RT-PCR with these primer sets is a reliable method for detecting PML/RAR alpha chimeric transcript in t(15; 17)-containing APL.
A unique mRNA produced in leukemic cells from a t(15;17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor alpha (RAR alpha) and a myeloid gene product called PML. PML contains a cysteine-rich region present in a new family of apparent DNA-binding proteins that includes a regulator of the interleukin-2 receptor gene (Rpt-1) and the recombination-activating gene product (RAG-1). Accordingly, PML may represent a novel transcription factor or recombinase. The aberrant PML-RAR fusion product, while typically retinoic acid responsive, displays both cell type- and promoter-specific differences from the wild-type RAR alpha. Because patients with APL can be induced into remission with high dose RA therapy, we propose that the nonliganded PML-RAR protein is a new class of dominant negative oncogene product. Treatment with RA would not only relieve this inhibition, but the activated PML-RAR protein may actually promote myelocyte differentiation.
Associated with 34464 Warrant Officer II John Richard Cousins, Australian Army. Born at Ballarat on 24 January 1926. Enlisted in 5 Battalion (CMF) on 15 October 1941 and transferred to the AIF on 29 July 1942. VX87342 Corporal Cousins served with 2/3 Pioneer Battalion on Tarakan from April to December 1945 and remained with the unit until 15 August 1946. Began course as a carpenter under the Commonwealth Reconstruction Training Scheme on 5 September 1946. Course terminated on 23 May 1950. Re-enlisted as a Private (3/400022) in the Regular Army Special Reserve (K Force) on 8 August 1950. Served with 9 Platoon, 3 RAR during the Korean War from September 1950 to October 1951. He was awarded the United States Bronze Star 'for courage in assaulting the enemy' during 3 RAR's first major action near Yongju on 22 October 1950. Transferred to the Australian Regular Army (34464) on 18 July 1952. Member (Corporal) of the Queen's Guard of the Australian Coronation Contingent from April to October 1953. Served with C Company, 2 RAR in Malaya from October 1955 to October 1957. Regimental Quartermaster Sergeant of 2 Commando Company (CMF) from 1958 to 1964. Transferred to 2 Battalion Pacific Islands Regiment(?). Promoted to Warrant Officer II in 1966. Awarded the Long Service & Good Conduct Medal in 1970. Volunteered and served in the Australian Army Training Team Vietnam from 1971-72. Awarded the Meritorious Service Medal in 1973. Discharged on 30 November 1976. Died 29 October 1991.
Research Academy Ruhr (RAR) is the cross-university platform for promoting early career researchers within the University Alliance Ruhr (UA Ruhr). Under RAR's umbrella, Ruhr-Universität Bochum (RUB), TU Dortmund University (TUDo), and the University of Duisburg-Essen (UDE) jointly offer an interdisciplinary qualification and networking program for the different stages of academic careers (doctoral research, Postdoc phase, Junior Faculty*).
Workshops, hands-on career and networking events as well as a mentoring program strengthen the development of personal and academic skills and prepare for a career in research, business, and society. The offers address the approximately 10,000 earlycareer researchers in the UA Ruhr and promote the mutual exchange of ideas, both within specific research fields and across individual disciplines.
The qualification program within RAR is a voluntary, interdisciplinary offer set up and coordinated by the local institutions for the promotion of early career researchers: RUB Research School, Graduate Center TUDo, and Graduate Center Plus of the UDE. Flyer: About Research Academy Ruhr (PDF)
RAR also promotes the visibility of UA Ruhr's excellent research conditions on an international level by hosting international postdocs as well as offering consultation sessions and workshops at career fairs all around the world.
* Junior Faculty includes all experienced Postdocs who are in one of the following qualification phases on their way to a professorship: habilitation candidates, junior group leaders, junior professors, tenure track professors.
RAR is a joint platform of the three UA Ruhr universities. It was built as a project from 2017 to 2021 and received funding by the Ministry of Culture and Science of North Rhine-Westphalia and the Mercator Research Centre Ruhr during this phase.
Research Academy Ruhr (RAR) is the cross-university platform of Ruhr-Universität Bochum, TU Dortmund University, and the University of Duisburg-Essen for promoting early career researchers in the University Alliance Ruhr (UA Ruhr).
Rebecca Edwards takes us back to the beginning of the nineteenth century when American deaf education emerged out of the eighteenth-century French schools for the deaf. Following the lead of French educators, Thomas H. Gallaudet and the French deaf teacher Laurent Clerc opened the American School for the Deaf in Hartford, Connecticut, in 1817. Under their direction, the school established manual signing as the sole educational method in their school and in other deaf schools they helped to found throughout the nation.
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