BackgroundChronic myeloid leukemia is characterized by a reciprocal translocation between chromosomes 9 and 22, creating the fusion gene BCR-ABL. The clinical significance of the type of BCR-ABL transcript in newly diagnosed patients in chronic phase treated with imatinib 400 mg from initial diagnosis remains unknown. Design and MethodsWe analyzed the clinical outcome of 78 newly diagnosed chronic phase patients, aged 16 or over, treated with imatinib 400 mg. Of these, 71 expressed either e13a2 or e14a2 transcripts. BCR-ABL transcripts were assayed by quantitative real-time polymerase chain reaction. ResultsAfter 12 months of treatment, 54% of the e14a2 patients had achieved a complete cytogenetic response, compared to 25% of the e13a2 patients (p=0.01). Kaplan-Meier analysis of the time to achieve complete cytogenetic response revealed that e14a2 patients had more rapid response rates, compared to e13a2 patients (p=0.006). e14a2 patients had a higher event-free survival rate in the first 12 months of treatment, although overall survival did not differ significantly between the patients with the two types of transcript. Human organic cation transporter protein 1 mRNA levels did not differ between the patients with the two types of transcript. The pre-treatment pCrKL/CrKL ratio (a surrogate marker of BCR-ABL tyrosine kinase activity) was higher in patients with e13a2 transcripts than in those with e14a2 (p=0.017). ConclusionsPatients expressing the e14a2 transcript type have a higher rate and more rapid complete cytogenetic responses than e13a2-expressing patients, which may be due to higher BCR-ABL tyrosine kinase activity. Knowledge of the transcript type may yield additional prognostic information, although this requires testing on larger datasets.Key words: chronic myeloid leukemia, BCR-ABL fusion transcript, imatinib. Haematologica 2009;94:1362-1367. doi:10.3324/haematol.2009 This is an open-access paper.

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Educational supervisors believe that the reformed curriculum in Liverpool is producing competent PRHOs who have been better prepared for the role of PRHO than previous graduates. It could be that uncertainty over knowledge base may be the price paid for reducing the factual burden and improving preparedness for professional practice.

In 1996 the University of Liverpool introduced a new curriculum based on the recommendations published in Tomorrow's Doctors. This work examines how graduates of that course view their undergraduate curriculum and whether they consider it prepared them well for the pre-registration year. Five focus groups were arranged with a selection of graduates from the first cohort to graduate from the reformed curriculum in order to ascertain their views on the course and how it had prepared them to work as pre-registration house officers (PRHOs). The focus groups were tape-recorded, transcribed and analysed. The PRHOs felt they had been well prepared for the PRHO year, citing the clinical experience of the final year, communication skills classes and the Clinical Skills Resource Centre as having been particularly beneficial. There were concerns about their basic science knowledge base although this had not affected their ability to work as PRHOs. They had criticisms of the way part of their course had been structured but overall they were happy with the content of the course. A reformed medical curriculum in the UK can prepare graduates well to work as junior doctors and can take away some of the anxiety associated with graduation; therefore, to that extent curriculum reform has worked. However, anxiety about undertaking the role of junior doctor seems to have been replaced by anxiety about knowledge base, despite having adequate knowledge to work as PRHOs. Students undertaking a reformed curriculum are wary about being the first people to use their training in the workplace. This factor may need to be considered when further reforms are introduced.