Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Introducing a reward system in assessment in histology: A comment on the learning strategies it might engender

BACKGROUND: Assessment, as an inextricable component of the curriculum, is an important factor influencing student approaches to learning. If assessment is to drive learning, then it must assess the desired outcomes. In an effort to alleviate some of the anxiety associated with a traditional discipline-based second year of medical studies, a bonus system was introduced into the Histology assessment. Students obtaining a year mark of 70% were rewarded with full marks for some tests, resulting in many requiring only a few percentage points in the final examination to pass Histology. METHODS: In order to ascertain whether this bonus system might be impacting positively on student learning, thirty-two second year medical students (non-randomly selected, representing four academic groups based on their mid-year results) were interviewed in 1997 and, in 1999, the entire second year class completed a questionnaire (n = 189). Both groups were asked their opinions of the bonus system. RESULTS: Both groups overwhelming voted in favour of the bonus system, despite less than 45% of students failing to achieve it. Students commented that it relieved some of the stress of the year-end examinations, and was generally motivating with regard to their work commitment. CONCLUSIONS: Being satisfied with how and what we assess in Histology, we are of the opinion that this reward system may contribute to engendering appropriate learning approaches (i.e. for understanding) in students. As a result of its apparent positive influence on learning and attitudes towards learning, this bonus system will continue to operate until the traditional programme is phased out. It is hoped that other educators, believing that their assessment is a reflection of the intended outcomes, might recognise merit in rewarding students for consistent achievement

Reframing professional development through understanding authentic professional learning

Continuing to learn is universally accepted and expected by professionals and other stakeholders across all professions. However, despite changes in response to research findings about how professionals learn, many professional development practices still focus on delivering content rather than enhancing learning. In exploring reasons for the continuation of didactic practices in professional development, this article critiques the usual conceptualization of professional development through a review of recent literature across professions. An alternative conceptualization is proposed, based on philosophical assumptions congruent with evidence about professional learning from seminal educational research of the past two decades. An argument is presented for a shift in discourse and focus from delivering and evaluating professional development programs to understanding and supporting authentic professional learning